Association of Vitamin D Receptor Gene Polymorphisms with Caries Risk: A Systematic Review and Meta-analysis

Association of Vitamin D Receptor Gene Polymorphisms with Caries Risk: A Systematic Review and Meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of Vitamin D Receptor Gene Polymorphisms with Caries Risk: A Systematic Review and Meta-analysis Xiurong Qin, Mei Wang, Linlin Wang, Ying Xu, Shijiang Xiong This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4147261/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Oct, 2024 Read the published version in BMC Pediatrics → Version 1 posted 15 You are reading this latest preprint version Abstract Background In this study, we aimed to evaluate the association of Vitamin D receptor (VDR) gene polymorphisms with caries risk in children (< 18 years). Methods The electronic databases PubMed, Cochrane, EMBASE, Web of Science, CNKI, Cqvip, and Wanfang were searched for observational studies on the relationship between VDR polymorphisms and caries, including cohort, case-control, and cross-sectional studies. Quality assessment of selected studies was conducted using the Newcastle Ottawa scale. Odds ratios (OR) with 95% confidence intervals (CI) values for associations of individual VDR polymorphisms with dental caries were calculated based on four genetic models: allelic, recessive, dominant, and overdominant. Of 79 studies considered, 10 (nine case-control and one cross-sectional) were selected for analysis; the studies involved seven VDR single nucleotide polymorphisms: rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820. Results Alleles C and T of rs10735810 were significantly differently distributed in the caries and caries-free groups (OR = 1.33, 95% CI: 1.30–2.30, P = 0.03), with CC + CT genotypes at this locus associated with greater risk of developing caries than the TT genotype (OR = 1.87, 95%CI: 1.15–3.04, P = 0.01). Further, TT + CC genotype at rs731236 was associated with a 1.33-fold higher risk of caries development than the TC genotype (OR = 1.33, 95%CI:1.06–1.67,P = 0.02). On subgroup analysis, the association between rs731236 and caries risk was affected by dentition type, ethnicity, and genotyping method (permanent dentition: OR = 1.48, 95%CI: 1.07–2.03, P = 0.02; Asian: OR = 1.38, 95%CI: 1.02–1.87, P = 0.03; quantitative PCR test: OR = 1.52, 95% CI: 1.10–2.10, P = 0.01). Genotype distributions at rs1544410, rs739837, rs2228570, and rs7975232 did not differ significantly between the caries and caries-free groups. Conclusions Caries risk was associated with rs731236 and rs10735810 genotypes, and rs731236 may be a risk factor for permanent teeth caries among Asian people. early childhood caries (ECC) vitamin D receptor (VDR) single nucleotide polymorphism (SNP) gene polymorphisms caries risk Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Globally, early childhood caries (ECC) is the most common childhood oral health problem and the most prevalent childhood disease, occurring five times more frequently than asthma, which ranks second in incidence [ 1 , 2 ] . The fourth epidemiological survey of oral diseases in China in 2015–2016 found that the prevalence rates of ECC were 50.8%, 63.6%, and 71.9% in 3-, 4-, and 5-year-olds, respectively [ 3 ] . Untreated ECC can not only cause local pain, abscesses, loss of teeth, malocclusion, and digestive dysfunction but can also harm the subsequent eruption of permanent teeth, leading to speech difficulties, which can seriously affect the psychological and physical health of children [ 4 – 6 ] ; hence, ECC is considered a major global public health problem that requires urgent resolution, and it is particularly important to provide genetic level evidence to inform early prevention. Nevertheless, dental caries is a multifactorial infectious disease. Microbial, behavioral, and environmental influences have been widely studied [ 7 , 8 ] , but these factors are insufficient to explain susceptibility to dental caries, since some people are more likely to develop caries than others when exposed to similar environmental risks [ 9 , 10 ] , suggesting that heredity may also contribute to susceptibility [ 11 ] . Indeed, it is estimated that > 40% of the risk of dental caries can be explained by genetic factors [ 12 ] ; however, despite the potential importance of genetic influences, only a few genes associated with susceptibility to caries have been verified to date, and the molecules they encode may be involved in enamel formation, mineralization, immune response, taste, and saliva [ 13 ] . Vitamin D plays a crucial role in the mineralization and deposition of enamel [ 14 ] . Further, the vitamin D receptor (VDR) gene, which maps to human chromosome 12q13.1, is important in regulating calcium and phosphorus metabolism, as well as cell growth and differentiation [ 15 , 16 ] . It has been proposed that the effects of vitamin D on dental caries may be meditated through serum 1,25(OH) 2 D 3 levels and VDR gene polymorphism since vitamin D levels are related to the occurrence of dental caries [ 17 , 18 ] , with insufficient vitamin D increasing the risk of their occurrence [ 19 ] ; however, few studies have explored the relationship between VDR gene polymorphism and dental caries. The VDR gene contains more than 200 polymorphic sites, among which the relationship with dental caries has been studied in seven single nucleotide polymorphisms (SNPs): rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820. In some previous studies, these variants were classified according to restriction enzyme sites (BsmI, TaqI, ApaI, and FokI, for rs1544410, rs731236, rs7975232, and rs10735810, respectively) or a transcription factor (CDX2) binding site (in rs11568820), affected by each polymorphism [ 20 – 23 ] . There have been reports that VDR polymorphisms at TaqI and FokI sites are associated with the occurrence of permanent dental caries [ 21 , 24 ] , while another report found that TaqI polymorphisms are not useful to predict dental caries susceptibility [ 25 ] . Hence, the relationship between VDR gene polymorphism and the risk of caries remains unclear, possibly due to the complexity of the risk factors for dental caries and the small sample sizes of individual studies resulting in low statistical power. Here, we conducted a systematic review of the relationship between VDR gene polymorphism and dental caries, to determine whether there are significant associations between these variants and dental caries, and to provide a theoretical basis for understanding the etiology of the condition and informing its primary prevention. Materials and methods Research question and study protocol This study was registered in the PROSPERO database (Registration number: CRD42022372202) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines [ 26 ] . The research question of this review was based on the PICOS framework, as follows: Population (P): subjects with or without caries under the age of 18; Intervention (I): with or without dental caries, confirmed by clinical examinations; Comparison (C): the distribution of VDR gene polymorphisms in caries and caries-free groups; Outcome (O): the association of VDR gene polymorphisms with caries risk; and Study Design (S): observational studies on the relationship between VDR gene polymorphism and caries, including cohort, case-control, and cross-sectional studies. Eligibility criteria Inclusion of articles focusing on the association between VDR polymorphisms and the risk of dental caries. Subjects > 18 years old were excluded. Reviews, abstracts, case reports and series, comments, letters to the editor, conference proceedings, in vitro investigations, and animal studies were also excluded. Literature search strategy and selection of papers The PubMed, Cochrane, EMBASE, Web of Science, CNKI, Cqvip, and Wanfang databases were searched for studies published in English or Chinese before August 31, 2022. The search strategies for each database are shown in Table 1 . Search results were imported into EndNote software (v 20.0), and duplicates were removed. The titles and abstracts of identified reports were checked by two authors (XR Qin and Y Xu), and any disagreement was resolved by consensus with a third author (LL Wang). References in relevant published articles were also manually searched. Research publications from the same authors or institutions were scrutinized to eliminate any data redundancy. In cases of redundancy, only results from the most recent publications were included. Table 1 Search strategy Database Key words Results PubMed ((vitamin D receptor gene polymorphism) and (dental caries)) or ((dental caries) AND (rs11568820)) or ((dental caries) AND (rs10735810)) or ((dental caries) AND (rs7975232)) or ((dental caries) AND (rs731236)) or ((dental caries) AND (rs1544410)) or ((dental caries) AND (CdX2)) or ((dental caries) AND (FokI)) or ((dental caries) AND (ApaI)) or ((dental caries) AND (TaqI)) or ((dental caries) AND (BsmI)) ((vitamin D receptor gene polymorphism) and (tooth decay)) or ((tooth decay) AND (rs11568820)) or ((tooth decay) AND (rs10735810)) or ((tooth decay) AND (rs7975232)) or ((tooth decay) AND (rs731236)) or ((tooth decay) AND (rs1544410)) or ((tooth decay) AND (CdX2)) or ((tooth decay) AND (FokI)) or ((tooth decay) AND (ApaI)) or ((tooth decay) AND (TaqI)) or ((tooth decay) AND (BsmI)) Last update posted on or before 08/31/2022 25 Web of Science ((vitamin D receptor gene polymorphism) and (dental caries)) or ((dental caries) AND (rs11568820)) or ((dental caries) AND (rs10735810)) or ((dental caries) AND (rs7975232)) or ((dental caries) AND (rs731236)) or ((dental caries) AND (rs1544410)) or ((dental caries) AND (CdX2)) or ((dental caries) AND (FokI)) or ((dental caries) AND (ApaI)) or ((dental caries) AND (TaqI)) or ((dental caries) AND (BsmI)) or ((vitamin D receptor gene polymorphism) and (tooth decay)) or ((tooth decay) AND (rs11568820)) or ((tooth decay) AND (rs731236)) or ((tooth decay) AND (rs7975232)) or ((tooth decay) AND (rs731236)) or ((tooth decay) AND (rs1544410)) or ((tooth decay) AND (CdX2)) or ((tooth decay) AND (FokI)) or ((tooth decay) AND (ApaI)) or ((tooth decay) AND (TaqI)) or ((tooth decay) AND (BsmI)) Last update posted on or before 08/31/2022 21 Cochrane Library ((vitamin D receptor gene polymorphism) and (dental caries)) or ((dental caries) AND (rs11568820)) or ((dental caries) AND (rs10735810)) or ((dental caries) AND (rs7975232)) or ((dental caries) AND (rs731236)) or ((dental caries) AND (rs1544410)) or ((dental caries) AND (CdX2)) or ((dental caries) AND (FokI)) or ((dental caries) AND (ApaI)) or ((dental caries) AND (TaqI)) or ((dental caries) AND (BsmI)) 1 Last update posted on or before 08/31/2022 Table 1 (continued). Search strategy Database Key words Results Embase (vitamin D receptor gene polymorphism) and (dental caries) (dental caries) AND (rs11568820) (dental caries) AND (rs10735810) (dental caries) AND (rs7975232) (dental caries) AND (rs731236) (dental caries) AND (rs1544410) (dental caries) AND (CdX2) (dental caries) AND (FokI) (dental caries) AND (ApaI) (dental caries) AND (TaqI) (dental caries) AND (BsmI) Last update posted on or before 08/31/2022 23 CNKI (“龋齿”or“龋病”) and (维生素D受体) and (多态性) (“龋齿”or“龋病”) and (“TaqI”or “ApaI”or“FokI”or“BsmI”or “CdX2”) (“龋齿”or“龋病”) and (“rs10735810”or“rs731236”or“rs1544410” or“rs7975232”or“rs11568820”) 截止日期: 2022年8月31日 3 Wanfang (龋齿)(维生素D受体) (多态性) (龋)(TaqI) + (龋)(ApaI) + (龋)(FokI) + (龋)(BsmI) + (龋)(CdX2) (龋)(rs10735810) + (龋)(rs731236) + (龋)(rs1544410) + (龋)(rs7975232) + (龋)(rs11568820) 截止日期: 2022年8月31日 3 Cqvip (龋齿)(维生素D受体) (多态性) (龋)(TaqI) + (龋)(ApaI) + (龋)(FokI) + (龋)(BsmI) + (龋)(CdX2) (龋)(rs10735810) + (龋)(rs731236) + (龋)(rs1544410) + (龋)(rs7975232) + (龋)(rs11568820) 截止日期: 2022年8月31日 2 Data extraction Relevant data were independently extracted from the included papers by two authors (XR Qin and Y Xu) in duplicate. Data extracted from the selected studies included study information (author, year, country, ethnicity, and study design), patient information (age, sample size, dentition type, and genotyping method), diagnostic information (diagnostic criteria for dental caries), and outcome information (VDR gene locus SNP loci and allele or genotype frequencies). To dichotomize the results of caries detection, the WHO 1997 [ 27 ] , WHO 2013 [ 28 ] , and ICDAS II [ 29 ] caries diagnostic criteria were combined to determine caries and caries-free classifications, where individuals classified as ICDAS = 0–2 and DMFT = 0 in WHO 1997 and WHO 2013 were considered the caries-free group, and those defined as ICDAS = 3–6 and DMFT > 0 in WHO 1997 and WHO 2013 considered the caries group. In the included articles, PCR-restriction fragment length polymorphism (RFLP) and real-time quantitative PCR were used to detect genotypes; polymorphisms detected by PCR-RFLP were named according to restriction endonuclease binding sites, while those identified by real-time quantitative PCR were named according to alleles at the polymorphic site. For convenience, the one-to-one correspondence between genotypes named using the two methods with minor allele frequency was determined (Table 2 ) and variables are hereafter referred to using their unique reference SNP identification numbers. Table 2 VDR SNP genotypes according to detection by the PCR-RFLP and real-time quantitative PCR detection method SNP Restriction endonuclease/transcription factor binding site(s) Allele PCR-RFLP Real-time quantitative PCR rs731236 TaqI T/C TT TT Tt TC tt CC rs739837 TaqI/BglI C/T TT TG GG rs10735810 FokI A/G FF CC Ff CT ff TT rs2228570 FokI A/G AA A > G AG GG rs7975232 ApaI A/C AA AA Aa AC Aa CC rs11568820 CDX2 A/G AA AA AG AG GG GG rs1544410 BsmI A/G BB AA Bb AG bb GG Quality assessment Quality assessment of included studies was carried out independently by two authors (XR Qin and Y Xu), and any disagreements were resolved by consensus. As included studies were all observational (nonrandomized), an accurate assessment of bias risk could not be conducted, and hence only quality was assessed. The Newcastle Ottawa scale (NOS), with minor modification, was used to assess the quality of the studies ( https://www.ohri.ca//programs/clinical_epidemiology/oxford.asp ), and added conformed to Hardy-Weinberg equilibrium. The NOS evaluates the methodological quality of each study, following a star system based on nine domains grouped into four main sets, namely, patient selection, comparability of study groups, outcome assessment, and Hardy-Weinberg equilibrium, and is scored by awarding a point for each answer. Studies were categorized as high quality, moderate quality, and low quality if they reached 7–9, 4–6, or 0–4 points, respectively (Table 3 ). Table 3 Quality assessment according to the Newcastle Ottawa scale Item Score criteria 1 Definition of caries a. Yes, the definition and diagnosis of caries are correct, independent, and valid ☆ b. Yes, such as according to medical records or the doctor’s own records ☆ c. No description 2 Disease representative a.Are consecutive cases, or cases are well represented ☆ b. Presence of selectivity bias or no description 3 Definition of the caries-free group a.No history of caries; patients to be studied☆ b.No description 4 Selection of the caries-free group a.Community control ☆ b.Hospital control c. No description 5 Comparability of cases and controls a.Controls selected and analyzed based on presence or absence of caries ☆ b.Controls selected and analyzed based on other factors 6 Exposure investigation and assessment methods a.Reliable records ☆ b.Blind interview ☆ c. Unblinded interview self-report or medical record only d. No description 7 The same investigation method a.Yes ☆ b.No 8 Nonresponse rate a.The nonresponse rate was the same in both groups ☆ b.No nonresponse rate was described c. Nonresponse rate was different, but no reason was stated 9 Conformed to Hardy-Weinberg equilibrium a.Hardy-Weinberg equilibrium ☆ b.Hardy-Weinberg disequilibrium Statistical analysis SPSS 22.0 software (SPSS, Inc., Chicago, IL, USA) was used to apply the Kappa test to evaluate agreement among reviewers in article identification, screening, data extraction, and quality. Meta-analysis was performed when warranted by the quality and quantity of included studies. Associations between VDR polymorphisms and caries were assessed by calculating odds ratio (OR) with 95% confidence interval (CI) values, based on four genetic models: allelic, recessive, dominant, and overdominant. Heterogeneity was assessed using the I 2 statistic and Cochrane’s Q test, with I 2 > 50% or P < 0.10 on Cochrane’s Q test, indicating substantial heterogeneity [ 30 ] . P < 0.05 was considered statistically significant. Publication bias was evaluated by visual inspection of funnel plots [ 30 ] , as well as by Egger’s and Begg’s tests. Sensitivity analyses (one study removed) were used to evaluate the stability of the results of analysis of data from included studies. Subgroup analyses, based on ethnicity, genotyping method, and tooth dentition, were conducted to determine the effects of subgroups on the overall results, if sufficient articles were included. Forest plots, subgroup analysis, and publication bias were conducted using Review manager 5 software (Revman5.4), while sensitivity analyses, Egger’s test, and Begg’s test were performed using Comprehensive Meta-Analysis version 3.0 (CMA 3.0) software. Results Systematic search The primary search identified 79 published papers, of which 14 satisfied the initial inclusion criteria. Reading of complete texts resulted in the inclusion of ten studies, of which nine were case-control studies [ 20 , 21 , 23 – 25 , 31 – 34 ] and one was a cross-sectional investigation [ 35 ] ; four studies were excluded because the subjects were older than 18 years [ 22 , 36 – 38 ] (Table S1 ). Details of the process for selection of research articles are presented as a flow diagram in Fig. 1 . Seven SNPs were involved in the selected studies: rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820 (Tables 4 and 5 ). Six studies reported data on rs731236 [ 20 , 21 , 23 – 25 , 33 ] , with 960 and 626 cases in the combined caries and control groups, respectively. Three studies reported data on rs739837 [ 32 , 34 , 35 ], with 461 and 335 cases in the respective combined caries and control groups. The rs10735810 SNP was included in three studies [ 20 , 21 , 23 ] , with 753 and 576 cases in the combined caries and control groups, respectively, and there were three studies on rs2228570 [ 32 , 34 , 35 ] , with 492 and 363 combined case and control group subjects, respectively. The rs7975232 locus was included in three studies [ 20 , 21 , 23 ] , with 752 cases in the combined caries group and 575 cases in the combined control group. There were four studies of rs1544410 [ 20 , 21 , 23 , 31 ] , with 1065 and 676 cases in the combined caries and controls groups, respectively. Finally, rs11568820 was included in one study [ 20 ] , with 303 cases in the caries group and 245 cases in the control group . Table 4 Basic characteristics of included articals Author Country Ethnicity Study design Age (years) Dentition Sample size Genotyping method SNPs Diagnostic criteria for caries NOS score Zhang(2006) [ 31 ] China Asian Case-control 6 ± 5.06 9 ± 3.12 Mixed Case: 312 Control: 100 PCR-RFLP rs1544410 - 6 Qin( 2019) [ 20 ] China Asian Case-control 3–5 Primary Case: 304 Control: 245 Real-Time PCR rs1544410 rs731236 rs7975232 rs10735810 rs11568820 WHO1997 8 Yu(2017) [ 21 ] China Asian Case-control 12 Permanent Case: 200 Control: 200 PCR-RFLP rs1544410 rs731236 rs7975232 rs10735810 WHO1997 7 Kong(2017) [ 23 ] China Asian Case-control 4–7 Primary Case: 249 Control: 131 PCR-RFLP rs1544410 rs731236 rs7975232 rs10735810 WHO1997 8 Holla(2017) [ 25 ] Czech Caucasian Case-control 13–15 Permanent Case: 235 Control: 153 Real-Time PCR rs731236 WHO1997 8 Cogulu(2016) [ 24 ] Turkey Caucasian Case-control 6–12 Mixed Case: 112 Control: 38 PCR-RFLP rs7975232 rs10735810 rs11568820 rs731236 WHO1997 7 Table 4 (continued). Basic characteristics of included artical Fatturi (2020) [ 35 ] Brazil Mixed cross-sectional 8 Mixed Case: 208 Control:132 Real-Time PCR rs739837 rs2228570 WHO2013 8 Aribam(2020) [ 33 ] India Asian Case-control 6–12 Mixed Case: 235 Control: 153 PCR-RFLP rs731236 WHO1997 7 Barbosa(2020) [ 32 ] Brazil Mixed Case-control 8–11 Mixed Case: 203 Control: 150 Real-Time PCR rs2228570 rs739837 ICDAS 8 Madalen(2020) [ 34 ] Brazil Mixed Case-control 6–13 Mixed Case: 138 Control: 19 Real-Time PCR rs2228570 rs739837 WHO 8 Table 5 Summary of VDR gene SNP allele and genotype data SNP Author(year) Caries-group(DMFT ≥ 1) Caries-free group(DMFT = 0) rs731236 TT TC CC T C TT TC CC T C Aribam(2020) [ 33 ] 22 25 13 69 51 26 23 11 75 45 Qin(2019) [ 20 ] 274 29 1 577 31 206 37 1 449 39 Kong(2017) [ 23 ] 230 19 0 479 19 120 11 0 251 11 Yu(2017) [ 21 ] 0 29 171 29 371 0 42 158 42 358 Holla(2017) [ 25 ] 95 110 30 300 170 51 85 17 187 119 Cogulu(2016) [ 24 ] 35 46 31 116 108 15 14 9 44 32 rs739837 Fatturi(2020) [ 35 ] TT TG GG T G TT TG GG T G 63 101 49 227 199 36 58 27 130 112 Barbosa(2020) [ 32 ] 45 77 27 167 131 65 92 45 222 182 Madalena(2020) [ 34 ] 34 52 13 120 78 5 6 1 16 8 rs10735810 Qin(2019) [ 20 ] CC CT TT C T CC CT TT C T 98 160 46 356 252 75 119 51 269 221 Yu(2017) [ 21 ] 86 96 18 268 132 65 86 49 216 184 Kong(2017) [ 23 ] 69 132 48 270 228 34 63 34 131 131 rs2228570 Fatturi(2020) [ 35 ] AA AG GG A G AA AG GG A G 22 85 97 129 279 13 63 56 89 175 Barbosa(2020) [ 32 ] 19 56 75 94 206 27 88 88 142 264 Madalena(2020) [ 34 ] 19 60 59 98 178 2 7 19 11 45 Table 5 (continued). Summary of VDR gene SNP allele and genotype data SNP Author Caries-group(DMFT ≥ 1) Caries-free group(DMFT = 0) rs1544410 Qin(2019) [ 20 ] AA AG GG A G AA AG GG A G 0 28 276 28 580 1 31 213 33 457 Yu(2017) [ 21 ] 0 36 164 36 364 0 31 169 31 369 Kong(2017) [ 23 ] 0 152 97 152 346 0 60 71 60 202 Zhang(2006) [ 31 ] 19 106 187 144 48 1 8 91 10 190 rs7975232 Qin(2019) [ 20 ] CC AC AA C A CC AC AA C A 157 129 17 443 163 123 100 21 346 142 Yu(2017) [ 21 ] 82 85 33 249 151 97 79 24 273 127 Kong(2017) [ 23 ] 118 87 44 323 175 70 43 18 183 79 rs11568820 AA AG GG A G AA AG GG A G Qin(2019) [ 20 ] 37 124 84 198 292 59 145 99 263 343 In Cogulu’s study [ 24 ] , FokI, ApaI and CDX2 had no significant difference between the case group and the control group, and the specific data of each genotype was not mentioned. Quality assessment and Kappa test Quality assessment of the included studies is shown in Table 3 . Overall, six studies were considered high quality [ 20 , 23 , 25 , 32 , 34 , 35 ] , and four were moderate quality [ 21 , 24 , 31 , 33 ] ; none was low quality (Tables 3 and 4 ). The Kappa coefficients of the reviewers involved in article identification and screening, data extraction, and quality assessment were 0.892, 0.893, and 1.000 (Table S2); hence, all had values of > 0.800, indicating strong agreement among reviewers [ 39 ] . Meta-analysis The rs11568820 locus was only included in one article [ 20 ] and was, therefore, not subjected to meta-analysis. The other six loci included in this study, namely, rs731236, rs739837, rs10735810, rs2228570, rs7975232, and rs1544410, were analyzed by meta-analysis. Subgroup analyses of rs731236 were also conducted, according to genotype detection method, ethnicity, and tooth dentition (primary, mixed, and permanent). The distribution of rs731236 T and C alleles did not differ significantly between subjects with and without caries (OR = 1.01, 95% CI: 0.83–1.21, P = 0.96); however, analysis under the overdominant genetic model showed that distribution of TT, TC, and CC genotypes differed significantly between subjects with and without caries, with the caries risk of the population with homozygous (TT or CC) genotypes 1.33-fold higher than that of the population with the heterozygous (TC) genotype (OR = 1.33, 95% CI: 1.06–1.67, P = 0.02). Heterogeneity testing indicated no significant heterogeneity among the studies (I 2 = 0%, P = 0.51). Further, sensitivity analysis showed that the combined effect magnitude did not change significantly after removal of any study, indicating that the results were reliable(Fig S1 ). Further, funnel plot, Egger’s test, and Begg’s tests revealed no evidence of publication bias in the included literature (Table 6 ; Fig. 2 and Fig. 3 a). Table 6 Results of meta-analysis of VDR SNPs alleles under different genetic models SNP Effect model OR(95%CI) Z P I2 P Begg test Egger test Sensitivity test rs731236 Allele(T VS.C) fixed 1.01 (0.83–1.21) 0.05 0.96 41% 0.13 0.71 0.62 no Recessive(TT VS. TC + CC) fixed 1.04(0.98,1.11) 1.40 0.16 18% 0.30 0.46 0.12 no Dominant(TT + TC VS. CC) fixed 0.75(0.54,1.05) 1.68 0.09 0.0% 0.95 0.81 0.21 no Overdominant(TT + CC VS. TC) fixed 1.33(1.06,1.67) 2.43 0.02 0.0% 0.51 0.26 0.07 no rs739837 Allele(T VS.C) fixed 1.00(0.81,1.23) 0.01 0.99 0.0% 0.81 0.29 0.24 no Recessive(TT VS. TG + GG) fixed 0.93(0.68,1.29) 0.43 0.67 0.0% 0.90 > 0.99 0.40 no Dominant(TT + TG VS. GG) fixed 1.09(0.76,1.58) 0.47 0.64 0.0% 0.63 > 0.99 0.60 no Overdominant(TT + GG VS. TG) fixed 0.89(0.66,1.20) 0.78 0.44 0.0% 0.70 > 0.99 0.94 no rs10735810 Allele(C VS. T) random 1.33(1.30, 2.30) 2.21 0.03 60.0% 0.08 > 0.99 0.71 no Recessive(CC VS. CT + TT) fixed 1.23(1.04,2.35) 1.70 0.09 4.0% 0.35 > 0.99 0.97 no Dominant(CC + CT VS. TT) random 1.87(1.15,3.04) 2.53 0.01 64.0% 0.06 0.30 0.32 yes Over-dominant(CC + TT VS. CT) fixed 0.83(0.67,1.04) 1.64 0.10 0.0% 0.99 > 0.99 0.26 no rs2228570 Allele(A VS.G) random 1.07(0.70,1.64) 0.32 0.75 68% 0.04 0.30 0.04 no Recessive(AA VS. AG + GG) fixed 1.09(0.70,1.71) 0.40 0.69 0.0% 0.64 0.30 0.11 no Dominant(AA + AG VS. GG) random 1.07(0.59,1.96) 0.23 0.82 73% 0.03 0.30 0.01 no Overdominant(AA + GG VS. AG) random 1.04(0.64,1.70) 0.15 0.88 58% 0.09 0.30 0.01 no Table 6 (continued). Results of meta-analysis of VDR SNPs alleles under different genetic models SNP Effect model OR(95%CI) Z P I2 P Begg test Egger test Sensitivity test rs7975232 Allele(C VS. A) random 0.89(0.70,1.14) 0.94 0.35 53% 0.12 > 0.99 0.39 no Recessive(CC VS. CA + AA) fixed 0.87(0.70,1.09) 1.21 0.23 8% 0.34 > 0.99 0.28 no Dominant(CC + CA VS. AA) random 0.91(0.55,1.50) 0.37 0.71 50% 0.13 0.30 0.14 no Overdominant(CC + AA VS. CA) fixed 0.91(0.73,1.14) 0.80 0.43 0.0% 0.98 > 0.999 0.57 no rs1544410 Allele(G VS. A) random 1.56(0.76,3.24) 1.21 0.23 89% 0.99 0.66 yes Recessive(GG VS. GA + AA) random 0.58(0.26,1.30) 1.33 0.18 89% 0.99 0.55 yes Recessive(GG VS. GA + AA)* random 0.86(0.48,1.54) 0.51 0.61 76% 0.02 0.296 0.292 no Overdominant(AA + GG VS. GA) random 0.60(0.28,1.25) 1.37 0.17 86% 0.99 0.56 yes Overdominant(AA + GG VS. GA)* random 0.45(0.48,1.49) 0.58 0.56 74% 0.02 0.296 0.266 no *Removed study of Zhang(2006) [ 28 ] Subgroup analysis of rs731236 demonstrated that caries risk was higher in subjects with homozygous (TT or CC) genotype, permanent dentition, and Asian ethnicity, genotyped by real-time quantitative PCR, than in those with heterozygous (TC) genotype, permanent dentition (OR = 1.48, 95% CI: 1.07–2.03, P = 0.02), and Asian ethnicity (OR = 1.38, 95% CI: 1.02–1.87, P = 0.03), genotyped by real-time quantitative PCR (OR = 1.52, 95% CI: 1.10–210, P = 0.01) (Table 7 – 9 ). Table 7 Subgroup meta-analysis of rs731236 alleles under different genetic models, according to dentition type Dentition Effect model OR(95%CI) Z P I2 P Allele(T VS.C) random 0.98(0.76–1.27) 0.12 0.90 41% 0.13 Primary 1.45(0.96–2.18) 1.76 0.08 0.0% 0.41 Mixed 0.80(0.55–1.15) 1.21 0.23 0.0% 0.92 Permanent 0.90(0.54–1.49) 0.41 0.68 68% 0.08 Recessive(TT VS. TC + CC) fixed 1.21(0.93–1.56) 1.40 0.16 18% 0.30 Primary 1.49(0.97–2.27) 1.83 0.07 0.0% 0.38 Mixed 0.73(0.43–1.24) 1.18 0.24 0.0% 0.88 Permanent 1.36(0.89–2.08) 1.41 0.16 - - Dominant(TT + TC VS. CC) fixed 0.75(0.54–1.05) 1.68 0.09 0.0% 0.95 Primary 1.25(0.08–20.04) 0.16 0.88 - - Mixed 0.81(0.44–1.51) 0.66 0.51 0.0% 1.00 Permanent 0.72(0.48–1.07) 1.61 0.11 0.0% 0.49 Over-dominant(TT + CC VS. TC) fixed 1.33(1.06–1.67) 2.43 0.02 0.0% 0.51 Primary 1.49(0.97–2.28) 1.82 0.07 0.0% 0.37 Mixed 0.85(0.50–1.45) 0.59 0.56 0.0% 0.94 Permanent 1.48(1.07–2.03) 2.37 0.02 0.0% 0.77 Table 8 Subgroup meta-analysis of rs731236 alleles under different genetic models, according to ethnicity Ethnicity Effect model OR(95%CI) Z P I2 P Allele(T VS.C) random 0.98(0.76–1.27) 0.12 0.90 41% 0.13 Asian 0.98(0.65–1.50) 0.07 0.94 57% 0.07 Caucasian 1.00(0.72–1.39) 0.01 0.99 28% 0.24 Recessive(TT VS. TC + CC) fixed 1.21(0.93–1.56) 1.41 0.16 27% 0.24 Asian 1.16(0.85–1.60) 0.72 0.47 37% 0.20 Caucasian 1.05(0.56–1.98) 0.16 0.88 55% 0.13 Dominant(TT + TC VS. CC) fixed 0.75(0.54–1.05) 1.68 0.09 0.0% 0.95 Asian 0.69(0.44–1.07) 1.65 0.10 0.0% 0.82 Caucasian 0.84(0.50–1.39) 0.68 0.50 0.0% 0.92 Over-dominant(TT + CC VS. T) fixed 1.33(1.06–1.67) 2.43 0.02 0.0% 0.51 Asian 1.38(1.02–1.87) 2.11 0.03 0.0% 0.45 Caucasian 1.26(0.88–1.80) 1.26 0.21 31% 0.23 Table 9 Subgroup meta-analysis of rs731236 alleles under different genetic models, according to genotype detection method Genotyping method Effect model OR（95%CI） Z P I2 P Allele (T VS.C) fixed 1.01(0.83-1.21） 0.05 0.96 41% 0.13 PCR-RFLP 0.79(0.60-1.04） 1.71 0.09 0.0% 0.75 Real-Time PCR 1.24(0.96-1.60） 1.67 0.10 36% 0.21 Recessive(TT VS. TC+CC) fixed 1.21(0.93-1.56） 1.41 0.16 27% 0.24 PCR-RFLP 1.49(0.97-2.27) 1.83 0.07 0.0% 0.38 Real-Time PCR 0.83(0.54-1.29) 0.82 0.41 0.0% 0.67 Dominant(TT+TC VS. CC) fixed 0.75（0.54-1.05） 1.68 0.09 0.0% 0.95 PCR-RFLP 0.70(0.47-1.05) 1.72 0.09 0.0% 0.84 Real-Time PCR 0.87(0.47-1.61) 0.44 0.66 0.0% 0.79 Over-dominant(TT+CC VS. TC) fixed 1.33(1.06-1.67) 2.43 0.02 0.0% 0.51 PCR-RFLP 1.15(0.83-1.60) 0.84 0.40 0.0% 0.46 Real-Time PCR 1.52(1.10-2.10) 2.56 0.01 0.0% 0.60 Funnel plot indicated that there was significant heterogeneity between the study by Yu et al. [ 16 ] and the other two included articles that analyzed rs10735810 SNP data; however, Begg’s (Z = 1.04, P = 0.30) and Egger’s (t = 1.83, P = 0.32) tests indicated that there was no publication bias in these articles; therefore, a random effects model was used to merge the quantitative effects reported by the studies (Table 6 ; Fig. 3 b and 4 ). The distribution of rs10735810 C and T alleles differed significantly between subjects with and without caries (OR = 1.33, 95% CI: 1.30–2.30, P = 0.03). Subjects with the CC + CT genotype had a significant 1.87-fold higher risk of caries than those with the TT genotype (OR = 1.87, 95% CI: 1.15–3.04, P = 0.01). The detection rate of the rs1544410 AA genotype in the population was low. Analysis under the recessive and overdominant models showed that there were no significant differences in the proportions of GG or GA genotypes between children with and without caries (recessive model: OR = 0.86, 95% CI: 0.48–1.54, P = 0.61; overdominant model: OR = 0.45, 95% CI: 0.48–1.49, P = 0.56); however, there was substantial heterogeneity among the included articles. Moreover, sensitivity analysis demonstrated that the combined effect magnitude was significantly altered by excluding data from either of the articles, Qin [ 20 ] or Zhang [ 31 ] (Table 6 ; Fig. 3 c and 5 ; Fig S3). Meta-analysis of the rs739837, rs2228570, and rs7975232 loci under recessive, dominant, and overdominant models demonstrated no significant differences in genotype distribution between the caries and noncaries groups (Table 6 ;Fig.S4-S12). Discussion This meta-analysis evaluated the relationship between VDR gene polymorphisms, including rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820, and risk of caries in subjects < 18 years old. We found that homozygous (TT or CC) genotype at the rs731236 locus was associated with a 1.33-fold higher risk of caries than the heterozygous (TC) genotype (OR = 1.33, 95% CI 1.06–1.67, P = 0.02), which differs from the findings of Lei et al. [ 40 ] In Lei’s study, rs731236 polymorphism with dental caries in the allele contrast model (C vs. T) and in the recessive genetic model (CC vs. TT/CT). This may be because, in our study, the subjects included were all ≤ 18 years old, and the oral environment, dietary habits, and microbial flora of adolescents differ from those in middle-aged and older adults [ 41 ] , who were also included in the study by Lei et al. Moreover, basal and induced VDR expression can be regulated by environmental, genetic, and epigenetic factors [ 42 ] , which may account for the observed differences in research results. Sadeghi et al. [ 43 ] found no significant difference in rs731236 between the two groups under an allelic model (T vs. C), similar to the findings of our study; however, under other genetic models, they also found no statistical difference between the two groups, which may be related to differences in meta-analysis effect models. Here, a fixed effect model was selected, according to the results of heterogeneity testing, while Sadeghi et al. used random effect models to analyze all inheritance models. Subgroup analysis of rs731236 among different ethnic groups found that homozygous (TT or CC) genotype was associated with a higher risk of caries than heterozygous (TC) genotype (OR = 1.38, 95% CI: 1.02–1.87, P = 0.03) under the overdominant genetic model in Asian populations, suggesting that homozygosity for this variant may be associated with caries risk in Asian populations, while no such correlation was found in the Caucasian population, consistent with the findings of Lei et al. [ 40 ] . These results may reflect regional and ethnic differences in the susceptibility to caries related to the rs731236 gene polymorphism. Bayram et al. [ 44 ] and Borilova et al. [ 45 ] showed that genetic factors can have different effects on enamel caries in primary and permanent teeth. An insertion/deletion polymorphism in the gene encoding angiotensin converting enzyme may be related to permanent tooth caries but not to primary tooth caries, especially in women in the Czech population [ 45 ] . This study found similar results, in that the homozygous (TT or CC) genotype of rs731236 was associated with a higher risk of dental caries in permanent teeth than the heterozygous (TC) genotype under the overdominant genetic model (OR = 1.48, 95% CI: 1.07–2.03, P = 0.02), similar to the findings of Lei et al. [ 40 ] , suggesting that genetic polymorphisms at the rs731236 locus are likely to affect the incidence of dental caries in permanent teeth but not in primary and mixed dentition. Among the ten reports included in our analysis, five [ 21 , 23 , 24 , 31 , 33 ] used the PCR-RFLP genotyping method, and five [ 20 , 25 , 32 , 34 , 35 ] used real-time quantitative PCR. The publication years of the PCR-RFLP studies were one in 2006 [ 31 ] , one in 2016 [ 24 ] , two in 2017 [ 21 , 23 ], and one in 2020 [ 33 ] , while all literature reporting real-time quantitative PCR genotyping data was published since 2017, with three papers published in 2020 [ 32 , 34 , 35 ] . Hence, the studies using real-time quantitative PCR genotyping were conducted more recently. This study found that, when using real-time quantitative PCR genotyping, the homozygous (TT or CC) genotype was associated with a higher risk of caries than the heterozygous (TC) genotype (OR = 1.52, 95% CI: 1.10–2.10, P = 0.01) in the overdominant genetic model, which may reflect the comparatively higher specificity of real-time quantitative PCR genotyping, which uses a closed tube mode to detect the target gene during amplification, with no requirement for further downstream steps, such as gel electrophoresis, which can increase the specificity of detection and reduce the possibility of cross-contamination, suggesting that the results of analysis of the rs731236 polymorphism may be affected by different genotype detection methods. Results of meta-analysis of rs10735810 allele and genotype data showed that C allele may be a risk factor for caries (OR = 1.33, 95% CI: 1.30–2.30, P = 0.03), with the risk of caries in subjects carrying the C allele 1.87-fold higher than that in subjects without the C allele (OR = 1.87, 95% CI: 1.15–3.04, P = 0.01). Sadeghi et al. [ 43 ] named genotypes at this locus based on restriction of endonuclease digestion sites. After one-to-one comparison, the results of this study were consistent with those of Sadeghi et al. [ 43 ] . The reason why rs10735810 is associated with susceptibility to caries may be related to the interaction of its cotranscription factors and its location in the gene structure [ 46 ] ; rs10735810 is located near the 5'-untranslated region of the VDR gene, within the DNA binding domain [ 47 – 50 ] , and the polymorphism changes the first potential start codon of the VDR gene, from ATG to ACG, resulting in a VDR protein truncated by three amino acids, which is more effective in transactivation of vitamin D target genes [ 51 ] . Although funnel plot analysis showed that there was heterogeneity between the findings of Yu et al. [ 21 ] and those of the other two included publications, Begg’s test (Z = 1.04, P = 0.30) and Egger’s test (t = 1.83, P = 0.32) indicated that there was no publication bias in these reports; our use of a random effects model to combine the effects can be expected to have mitigated the interference on the results of heterogeneity among the included studies to some extent. The rate of detection of the AA genotype at rs1544410 is low; three articles found no AA genotypes at this locus in the groups with caries [ 20 , 21 , 23 ] , and there were also no individuals with this genotype in the group without caries in two studies [ 21 , 23 ] . The results of analysis under recessive and overdominant models showed that there were no significant differences in the proportions of GG or GA genotypes at rs1544410 between subjects with and without caries (OR = 0.86, 95% CI: 0.48–1.54, P = 0.61; OR = 0.45, 95%CI: 0.48–1.49, P = 0.56), suggesting that this locus may not be related to the risk of caries; however, studies including rs1544410 were highly heterogeneous. Sensitivity analysis found that if either of the studies by Qin et al. [ 20 ] or Zhang et al. [ 31 ] were excluded, the magnitude of the combined effect changed significantly, but due to the limited number of articles included, more reliable results could not be obtained by eliminating articles. More new evidence is needed to further assess the correlation between the rs1544410 variant and the risk of caries. The results of meta-analysis of allelic, recessive, dominant, and overdominant models at rs739837, rs2228570, and rs7975232 revealed no significant differences in genotype distributions between the caries and caries-free groups, consistent with the findings of Sadeghi et al. [ 43 ] , suggesting that these polymorphisms are unlikely to be related to the risk of caries in children. The meta-analysis had several limitations. Firstly, the studies included in this study are mainly case-control studies. Some studies showed mismatched sample sizes between case and control groups, and these bias risks may not be avoided; Secondly, data on the SNP (rs11568820) were not subjected to meta-analysis because they were only reported in one article. Further research confirmation is needed from different races and regions. Finally, only one article studied linkage disequilibrium (LD) analysis [ 21 ] . In this article, four SNPs (rs7975232, rs1544410, rs731236, rs10735810) showed strong evidence of recombination except for rs731236 and rs1544410 in caries group data. But the linkage of rs731236 and rs1544410 in caries group still did not reach a strong LD level. Despite the above limitations, this meta-analysis still has the following advantages: all study subjects met the Hardy-Weinbery equilibrium, the included studies involved a wide geographical distribution and different types of dentition, and all included studies had high quality scores. Therefore, this meta-analysis is a reasonable summary of the current published research findings and leads to more reliable conclusions. Conclusion The rs10735810 and rs731236 variants were related to caries risk, and the association of rs731236 with caries risk may be affected by dentition type, ethnicity, and genotype detection method. These findings imply that rs731236 has potential as an indicator of risk of caries in permanent dentition among Asian people, and that rs10735810 may also be an indicator of caries. The rs739837, rs2228570, and rs7975232 variants may not be associated with the risk of caries. Further, the evidence does not support an association of rs1544410 with risk of caries, but this finding requires further confirmation. Abbreviations VDR Vitamin D receptor OR Odds ratios CI confidence intervals ECC early childhood caries SNP single nucleotide polymorphism NOS The Newcastle Ottawa scale LD linkage disequilibrium Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Funding Supported by Assistant Research Fund for the president of Jinan Stomatological Hospital (2019-05). Authors' contributions Study design: XR Qin, Y Xu and M Wang. Database searched, data extraction and data synthesis: XR Qin and M Wang. Initial manuscript draft: XR Qin, and M Wang. Critical revision of the manuscript: XR Qin, Y Xu, LL Wang and SJ Xiong. All authors read and approved the final version of the manuscript. XR Qin and M Wang contributed to the work equally. Acknowledgement The authors would like to thank Dr Qingchun Yao for the work of this review of evidence. References Benjamin R M. Oral health: the silent epidemic[J]. Public Health Rep, 2010,125(2):158-159. Petersen P E, Bourgeois D, Ogawa H, et al. The global burden of oral diseases and risks to oral health[J]. Bull World Health Organ, 2005,83(9):661-669. Du MQ, Li Z, Jiang H, et al. Dental Caries Status and its Associated Factors among 3- to 5-year-old Children in China: A National Survey[J]. Chin J Dent Res, 2018,21(3):167-179. Sun H B, Zhang W, Zhou X B. Risk Factors associated with Early Childhood Caries[J]. Chin J Dent Res, 2017,20(2):97-104. Sheiham A. Dental caries affects body weight, growth and quality of life in pre-school children[J]. Br Dent J, 2006,201(10):625-626. Finlayson T L, Siefert K, Ismail A I, et al. Psychosocial factors and early childhood caries among low-income African-American children in Detroit[J]. Community Dent Oral Epidemiol, 2007,35(6):439-448. Selwitz R H, Ismail A I, Pitts N B. Dental caries[J]. Lancet, 2007,369(9555):51-59. Qin M, Li J, Zhang S, et al. Risk factors for severe early childhood caries in children younger than 4 years old in Beijing, China[J]. Pediatr Dent, 2008,30(2):122-128. Yildiz G, Ermis R B, Calapoglu N S, et al. Gene-environment Interactions in the Etiology of Dental Caries[J]. J Dent Res, 2016,95(1):74-79. Gustafsson B E, Quensel C E, Lanke L S, et al. The Vipeholm dental caries study; the effect of different levels of carbohydrate intake on caries activity in 436 individuals observed for five years[J]. Acta Odontol Scand, 1954,11(3-4):232-264. Piekoszewska-Zietek P, Turska-Szybka A, Olczak-Kowalczyk D. Single Nucleotide Polymorphism in the Aetiology of Caries: Systematic Literature Review[J]. Caries Res, 2017,51(4):425-435. Bretz W A, Corby P M, Schork N J, et al. Longitudinal analysis of heritability for dental caries traits[J]. J Dent Res, 2005,84(11):1047-1051. Vieira A R, Modesto A, Marazita M L. Caries: review of human genetics research[J]. Caries Res, 2014,48(5):491-506. Berdal A, Lezot F, Nefussi J R, et al. Mineralized dental tissues: a unique example of skeletal biodiversity derived from cephaic neural crest[J]. Morphologie, 2000,84(265):5-10. Valdivielso J M, Fernandez E. Vitamin D receptor polymorphisms and diseases[J]. Clin Chim Acta, 2006,371(1-2):1-12. Mesbah M, Nemere I, Papagerakis P, et al. Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization[J]. J Bone Miner Res, 2002,17(9):1588-1596. Schroth R J, Jeal N S, Kliewer E, et al. The relationship between vitamin D and severe early childhood caries: a pilot study[J]. Int J Vitam Nutr Res, 2012,82(1):53-62. Theodoratou E, Tzoulaki I, Zgaga L, et al. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials[J]. BMJ, 2014,348:g2035. Hujoel P P. Vitamin D and dental caries in controlled clinical trials: systematic review and meta-analysis[J]. Nutr Rev, 2013,71(2):88-97. Qin X, Shao L, Zhang L, et al. Investigation of Interaction between Vitamin D Receptor Gene Polymorphisms and Environmental Factors in Early Childhood Caries in Chinese Children[J]. Biomed Res Int, 2019,2019:4315839. Yu M, Jiang Q Z, Sun Z Y, et al. Association between Single Nucleotide Polymorphisms in Vitamin D Receptor Gene Polymorphisms and Permanent Tooth Caries Susceptibility to Permanent Tooth Caries in Chinese Adolescent[J]. Biomed Res Int, 2017,2017:4096316. Hu X P, Li Z Q, Zhou J Y, et al. Analysis of the association between polymorphisms in the vitamin D receptor (VDR) gene and dental caries in a Chinese population[J]. Genet Mol Res, 2015,14(3):11631-11638. Kong Y Y, Zheng J M, Zhang W J, et al. The relationship between vitamin D receptor gene polymorphism and deciduous tooth decay in Chinese children[J]. BMC Oral Health, 2017,17(1):111. Cogulu D, Onay H, Ozdemir Y, et al. The Role of Vitamin D Receptor Polymorphisms on Dental Caries[J]. J Clin Pediatr Dent, 2016,40(3):211-214. Izakovicova H L, Borilova L P, Kastovsky J, et al. Vitamin D Receptor TaqI Gene Polymorphism and Dental Caries in Czech Children[J]. Caries Res, 2017,51(1):7-11. Page M J, Mckenzie J E, Bossuyt P M, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews[J]. BMJ, 2021,372:n71. World Health Organization: Oral health surveys: basic methods[J]. Geneva: World Health Organization, 1997. World Health Organization: Oral health surveys: basic methods[J]. Geneva: World Health Organization, 2013. Shoaib L, Deery C, Ricketts D N, et al. Validity and reproducibility of ICDAS II in primary teeth[J]. Caries Res, 2009,43(6):442-448. Sutton A J, Duval S J, Tweedie R L, et al. Empirical assessment of effect of publication bias on meta-analyses[J]. BMJ, 2000,320(7249):1574-1577. Zhang,L.,Sun L.W., Study on the relationship between caries and vitamin D receptor gene polymorphism in children in Changchun. ZHONGGUO FUYOU BAOJIAN, 2006(04): 541-543.. Barbosa M, Lima D C, Reis C, et al. Vitamin D receptor FokI and BglI genetic polymorphisms, dental caries, and gingivitis[J]. Int J Paediatr Dent, 2020,30(5):642-649. Aribam V G, Aswath N, Ramanathan A. Single-nucleotide polymorphism in Vitamin D receptor gene and its association with dental caries in children[J]. J Indian Soc Pedod Prev Dent, 2020,38(1):8-13. Madalena I, Xavier T, Cruz G, et al. Evaluation of vitamin D receptor genetic polymorphisms with dental caries and developmental defects of enamel in Brazilian children.[J]. Pediatric Dental Journal, 2020,3(30):161-166. Fatturi A L, Menoncin B L, Reyes M T, et al. The relationship between molar incisor hypomineralization, dental caries, socioeconomic factors, and polymorphisms in the vitamin D receptor gene: a population-based study[J]. Clin Oral Investig, 2020,24(11):3971-3980. Li Z.Q, et al., A study on the association of the gene polymorphisms of vitamin D receptor with dental caries susceptibility in Dongxiang and Bao'an minorities in Gansu province. Journal of Practical Stomatology, 2013. 29(4): 535-538. Nireeksha N, Hegde M N, Shetty S S, et al. FOK l Vitamin D Receptor Gene Polymorphism and Risk of Dental Caries: A Case-Control Study[J]. Int J Dent, 2022,2022:6601566. Protyusha G B, Sundharam B S. Analysis of the association between polymorphisms in Vitamin D receptor gene and dental caries[J]. Indian J Dent Res, 2021,32(1):3-7. Landis J R, Koch G G. The measurement of observer agreement for categorical data[J]. Biometrics, 1977,33(1):159-174. Lei W, Tian H, Xia Y. Association Between the TaqI (rs731236 T>C) Gene Polymorphism and Dental Caries Risk: A Meta-analysis[J]. Genet Test Mol Biomarkers, 2021,25(5):368-375. Burcham Z M, Garneau N L, Comstock S S, et al. Patterns of Oral Microbiota Diversity in Adults and Children: A Crowdsourced Population Study[J]. Sci Rep, 2020,10(1):2133. Saccone D, Asani F, Bornman L. Regulation of the vitamin D receptor gene by environment, genetics and epigenetics[J]. Gene, 2015,561(2):171-180. Sadeghi M, Golshah A, Godiny M, et al. The Most Common Vitamin D Receptor Polymorphisms (ApaI,FokI, TaqI, BsmI, and BglI) in Children with Dental Caries: A Systematic Review and Meta-Analysis[J]. Children (Basel), 2021,8(4). Bayram M, Deeley K, Reis M F, et al. Genetic influences on dental enamel that impact caries differ between the primary and permanent dentitions[J]. Eur J Oral Sci, 2015,123(5):327-334. Borilova L P, Kastovsky J, Bartosova M, et al. ACE Insertion/Deletion Polymorphism Associated with Caries in Permanent but Not Primary Dentition in Czech Children[J]. Caries Res, 2016,50(2):89-96. Tanaka K, Miyake Y, Hanioka T, et al. VDR gene polymorphisms, interaction with smoking and risk of periodontal disease in Japanese women: the Kyushu Okinawa maternal and child health study[J]. Scand J Immunol, 2013,78(4):371-377. Kanan R M, Varanasi S S, Francis R M, et al. Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density in healthy male subjects[J]. Clin Endocrinol (Oxf), 2000,53(1):93-98. Ingles S A, Wang J, Coetzee G A, et al. Vitamin D receptor polymorphisms and risk of colorectal adenomas (United States)[J]. Cancer Causes Control, 2001,12(7):607-614. Chen H Y, Chen W C, Hsu C D, et al. Relation of vitamin D receptor FokI start codon polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal women in Taiwan[J]. Acta Obstet Gynecol Scand, 2002,81(2):93-98. Tworoger S S, Gates M A, Lee I M, et al. Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies[J]. Cancer Res, 2009,69(5):1885-1891. Arai H, Miyamoto K, Taketani Y, et al. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women[J]. J Bone Miner Res, 1997,12(6):915-921. Additional Declarations No competing interests reported. Supplementary Files 2024.4.1.zip Supplementarymaterial.zip Cite Share Download PDF Status: Published Journal Publication published 11 Oct, 2024 Read the published version in BMC Pediatrics → Version 1 posted Editorial decision: Revision requested 31 Jul, 2024 Reviews received at journal 21 Jul, 2024 Reviews received at journal 19 Jul, 2024 Reviews received at journal 19 Jul, 2024 Reviewers agreed at journal 17 Jul, 2024 Reviews received at journal 16 Jul, 2024 Reviewers agreed at journal 16 Jul, 2024 Reviewers agreed at journal 10 Jul, 2024 Reviewers agreed at journal 10 Jul, 2024 Reviewers agreed at journal 10 Jul, 2024 Reviewers invited by journal 10 Jul, 2024 Editor assigned by journal 20 Jun, 2024 Editor invited by journal 03 Apr, 2024 Submission checks completed at journal 03 Apr, 2024 First submitted to journal 22 Mar, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4147261","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":285885289,"identity":"5040f529-b575-4667-b3af-185619d14127","order_by":0,"name":"Xiurong Qin","email":"","orcid":"","institution":"Shanghai Stomatological Hospital Fudan University","correspondingAuthor":false,"prefix":"","firstName":"Xiurong","middleName":"","lastName":"Qin","suffix":""},{"id":285885292,"identity":"0d44f5e0-675b-4385-99bb-6d881c6d64ae","order_by":1,"name":"Mei Wang","email":"","orcid":"","institution":"Qilu Hospital of Shandong University Dezhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mei","middleName":"","lastName":"Wang","suffix":""},{"id":285885295,"identity":"79446b92-e991-4eed-a4f6-6487086751eb","order_by":2,"name":"Linlin Wang","email":"","orcid":"","institution":"Jinan Stomatological Hospital","correspondingAuthor":false,"prefix":"","firstName":"Linlin","middleName":"","lastName":"Wang","suffix":""},{"id":285885298,"identity":"681811b1-43c3-4636-b328-d2518c45f39b","order_by":3,"name":"Ying Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYBACfmb+h49/VLDJ8bM3EKlFsp2H2ZjhDJ+xZM8BIrUYnOdhE2ZskUvccCOBWFuaeY8xFzaYJW64+XjjDYYam2iCWviZ+dIez9yRZjzzdlqxBcOxtNwGwrYwmBvwnjkm23c7x0yCseEwYS0GhxnMJHjb/jM23DxDtBYeM2neNjbFCTd4iNQi2cyWbDjjDBswkIF+SSDGL/z8hw8++ACOysMbb3yosSGsBcWREgmkKIdoIVXHKBgFo2AUjAwAAKmMQOYgx2xdAAAAAElFTkSuQmCC","orcid":"","institution":"Jinan Stomatological Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ying","middleName":"","lastName":"Xu","suffix":""},{"id":285885299,"identity":"a3efed41-10e5-4794-bf0c-39c486f319d9","order_by":4,"name":"Shijiang Xiong","email":"","orcid":"","institution":"Department of VIP Center, School and Hospital of Stomatology, Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Shijiang","middleName":"","lastName":"Xiong","suffix":""}],"badges":[],"createdAt":"2024-03-22 05:43:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4147261/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4147261/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12887-024-05127-w","type":"published","date":"2024-10-11T15:57:39+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":53879352,"identity":"48a1bb7a-5c76-41ad-beca-719c265c044f","added_by":"auto","created_at":"2024-04-01 17:08:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47079,"visible":true,"origin":"","legend":"\u003cp\u003ePRISMA flow diagram summarizing the study selection process\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/24797232402faf9d41c19fe7.png"},{"id":53879360,"identity":"458d6c96-898d-4d0f-9a2b-82301c1ddc85","added_by":"auto","created_at":"2024-04-01 17:08:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":566630,"visible":true,"origin":"","legend":"\u003cp\u003eThe rs731236 polymorphism and caries risk (meta-analysis forest plot)\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/d172999bc3b4e91c350e0c05.png"},{"id":53879355,"identity":"dc4d9832-1bbe-46d1-baa8-2cc453f210da","added_by":"auto","created_at":"2024-04-01 17:08:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":283204,"visible":true,"origin":"","legend":"\u003cp\u003eFunnel plot of publication bias between VDR gene SNPs and caries risk: (a) rs731236, (b) rs10735810, and (c) rs1544410\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/191e427dd37561fea430cc98.png"},{"id":53879661,"identity":"b1e4a0f0-a9b7-42d0-a3e4-55c124c6aa46","added_by":"auto","created_at":"2024-04-01 17:16:13","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":357505,"visible":true,"origin":"","legend":"\u003cp\u003eThe rs10735810 polymorphism and caries risk (meta-analysis forest plot)\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/b51b517387f2f118dd83064e.png"},{"id":53879354,"identity":"4a3f807b-a8f3-4562-bc02-24476c1339c7","added_by":"auto","created_at":"2024-04-01 17:08:12","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":852664,"visible":true,"origin":"","legend":"\u003cp\u003eThe rs1544410 polymorphism and caries risk (meta-analysis forest plot)\u003c/p\u003e","description":"","filename":"Fig.5.png","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/e3f9dcc4d51d9fa26a8f8167.png"},{"id":66597728,"identity":"649a17e9-d3e3-4451-abfc-d6c57df88ee0","added_by":"auto","created_at":"2024-10-14 16:11:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3337232,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/7c2dcc3f-1619-4656-9120-522054a016f1.pdf"},{"id":53879361,"identity":"07ec6250-04c9-4e03-a991-efecffb1f225","added_by":"auto","created_at":"2024-04-01 17:08:14","extension":"zip","order_by":11,"title":"","display":"","copyAsset":false,"role":"supplement","size":4293007,"visible":true,"origin":"","legend":"","description":"","filename":"2024.4.1.zip","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/1abf985fba38af29e318c206.zip"},{"id":53879358,"identity":"fd595f75-0f01-43e3-b461-22c8277013fd","added_by":"auto","created_at":"2024-04-01 17:08:13","extension":"zip","order_by":18,"title":"","display":"","copyAsset":false,"role":"supplement","size":4164511,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterial.zip","url":"https://assets-eu.researchsquare.com/files/rs-4147261/v1/e16f2fae215e7b15bfc34d76.zip"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of Vitamin D Receptor Gene Polymorphisms with Caries Risk: A Systematic Review and Meta-analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlobally, early childhood caries (ECC) is the most common childhood oral health problem and the most prevalent childhood disease, occurring five times more frequently than asthma, which ranks second in incidence\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The fourth epidemiological survey of oral diseases in China in 2015\u0026ndash;2016 found that the prevalence rates of ECC were 50.8%, 63.6%, and 71.9% in 3-, 4-, and 5-year-olds, respectively\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/sup\u003e. Untreated ECC can not only cause local pain, abscesses, loss of teeth, malocclusion, and digestive dysfunction but can also harm the subsequent eruption of permanent teeth, leading to speech difficulties, which can seriously affect the psychological and physical health of children\u003csup\u003e[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e; hence, ECC is considered a major global public health problem that requires urgent resolution, and it is particularly important to provide genetic level evidence to inform early prevention.\u003c/p\u003e \u003cp\u003eNevertheless, dental caries is a multifactorial infectious disease. Microbial, behavioral, and environmental influences have been widely studied\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e, but these factors are insufficient to explain susceptibility to dental caries, since some people are more likely to develop caries than others when exposed to similar environmental risks\u003csup\u003e[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e, suggesting that heredity may also contribute to susceptibility\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Indeed, it is estimated that \u0026gt;\u0026thinsp;40% of the risk of dental caries can be explained by genetic factors\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e; however, despite the potential importance of genetic influences, only a few genes associated with susceptibility to caries have been verified to date, and the molecules they encode may be involved in enamel formation, mineralization, immune response, taste, and saliva\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eVitamin D plays a crucial role in the mineralization and deposition of enamel\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Further, the vitamin D receptor (VDR) gene, which maps to human chromosome 12q13.1, is important in regulating calcium and phosphorus metabolism, as well as cell growth and differentiation\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. It has been proposed that the effects of vitamin D on dental caries may be meditated through serum 1,25(OH)\u003csub\u003e2\u003c/sub\u003eD\u003csub\u003e3\u003c/sub\u003e levels and VDR gene polymorphism since vitamin D levels are related to the occurrence of dental caries\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e, with insufficient vitamin D increasing the risk of their occurrence\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e; however, few studies have explored the relationship between VDR gene polymorphism and dental caries. The VDR gene contains more than 200 polymorphic sites, among which the relationship with dental caries has been studied in seven single nucleotide polymorphisms (SNPs): rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820. In some previous studies, these variants were classified according to restriction enzyme sites (BsmI, TaqI, ApaI, and FokI, for rs1544410, rs731236, rs7975232, and rs10735810, respectively) or a transcription factor (CDX2) binding site (in rs11568820), affected by each polymorphism\u003csup\u003e[\u003cspan additionalcitationids=\"CR21 CR22\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. There have been reports that VDR polymorphisms at TaqI and FokI sites are associated with the occurrence of permanent dental caries\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e, while another report found that TaqI polymorphisms are not useful to predict dental caries susceptibility\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e. Hence, the relationship between VDR gene polymorphism and the risk of caries remains unclear, possibly due to the complexity of the risk factors for dental caries and the small sample sizes of individual studies resulting in low statistical power.\u003c/p\u003e \u003cp\u003eHere, we conducted a systematic review of the relationship between VDR gene polymorphism and dental caries, to determine whether there are significant associations between these variants and dental caries, and to provide a theoretical basis for understanding the etiology of the condition and informing its primary prevention.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eResearch question and study protocol\u003c/h2\u003e \u003cp\u003eThis study was registered in the PROSPERO database (Registration number: CRD42022372202) and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. The research question of this review was based on the PICOS framework, as follows: Population (P): subjects with or without caries under the age of 18; Intervention (I): with or without dental caries, confirmed by clinical examinations; Comparison (C): the distribution of VDR gene polymorphisms in caries and caries-free groups; Outcome (O): the association of VDR gene polymorphisms with caries risk; and Study Design (S): observational studies on the relationship between VDR gene polymorphism and caries, including cohort, case-control, and cross-sectional studies.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEligibility criteria\u003c/h2\u003e \u003cp\u003eInclusion of articles focusing on the association between VDR polymorphisms and the risk of dental caries. Subjects\u0026thinsp;\u0026gt;\u0026thinsp;18 years old were excluded. Reviews, abstracts, case reports and series, comments, letters to the editor, conference proceedings, in vitro investigations, and animal studies were also excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eLiterature search strategy and selection of papers\u003c/h2\u003e \u003cp\u003eThe PubMed, Cochrane, EMBASE, Web of Science, CNKI, Cqvip, and Wanfang databases were searched for studies published in English or Chinese before August 31, 2022. The search strategies for each database are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Search results were imported into EndNote software (v 20.0), and duplicates were removed. The titles and abstracts of identified reports were checked by two authors (XR Qin and Y Xu), and any disagreement was resolved by consensus with a third author (LL Wang). References in relevant published articles were also manually searched. Research publications from the same authors or institutions were scrutinized to eliminate any data redundancy. In cases of redundancy, only results from the most recent publications were included.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSearch strategy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDatabase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKey words\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eResults\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePubMed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e((vitamin D receptor gene polymorphism) and (dental caries)) or ((dental caries) AND (rs11568820)) or ((dental caries) AND (rs10735810)) or ((dental caries) AND (rs7975232)) or ((dental caries) AND (rs731236)) or ((dental caries) AND (rs1544410)) or ((dental caries) AND (CdX2)) or ((dental caries) AND (FokI)) or ((dental caries) AND (ApaI)) or ((dental caries) AND (TaqI)) or ((dental caries) AND (BsmI))\u003c/p\u003e \u003cp\u003e((vitamin D receptor gene polymorphism) and (tooth decay)) or ((tooth decay) AND (rs11568820)) or ((tooth decay) AND (rs10735810)) or ((tooth decay) AND (rs7975232)) or ((tooth decay) AND (rs731236)) or ((tooth decay) AND (rs1544410)) or ((tooth decay) AND (CdX2)) or ((tooth decay) AND (FokI)) or ((tooth decay) AND (ApaI)) or ((tooth decay) AND (TaqI)) or ((tooth decay)\u0026nbsp;AND (BsmI))\u003c/p\u003e \u003cp\u003eLast update posted on or before 08/31/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeb of Science\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e((vitamin D receptor gene polymorphism) and (dental caries)) or ((dental caries) AND (rs11568820)) or ((dental caries) AND (rs10735810)) or ((dental caries) AND (rs7975232)) or ((dental caries) AND (rs731236)) or ((dental caries) AND (rs1544410)) or ((dental caries) AND (CdX2)) or ((dental caries) AND (FokI)) or ((dental caries) AND (ApaI)) or ((dental caries) AND (TaqI)) or ((dental caries)\u0026ensp;AND (BsmI))\u0026ensp;or ((vitamin D receptor gene polymorphism) and (tooth decay)) or ((tooth decay) AND (rs11568820)) or ((tooth decay) AND (rs731236)) or ((tooth decay) AND (rs7975232)) or ((tooth decay) AND (rs731236)) or ((tooth decay) AND (rs1544410)) or ((tooth decay) AND (CdX2)) or ((tooth decay) AND (FokI)) or ((tooth decay) AND (ApaI)) or ((tooth decay) AND (TaqI)) or ((tooth decay)\u0026ensp;AND (BsmI))\u003c/p\u003e \u003cp\u003eLast update posted on or before 08/31/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCochrane Library\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e((vitamin D receptor gene polymorphism) and (dental caries)) or ((dental caries) AND (rs11568820)) or ((dental caries) AND (rs10735810)) or ((dental caries) AND (rs7975232)) or ((dental caries) AND (rs731236)) or ((dental caries) AND (rs1544410)) or ((dental caries) AND (CdX2)) or ((dental caries) AND (FokI)) or ((dental caries) AND (ApaI)) or ((dental caries) AND (TaqI)) or ((dental caries) AND (BsmI))\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLast update posted on or before 08/31/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e(continued). Search strategy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDatabase\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eKey words\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eResults\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmbase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(vitamin D receptor gene polymorphism) and (dental caries)\u003c/p\u003e \u003cp\u003e(dental caries) AND (rs11568820)\u003c/p\u003e \u003cp\u003e(dental caries) AND (rs10735810)\u003c/p\u003e \u003cp\u003e(dental caries) AND (rs7975232)\u003c/p\u003e \u003cp\u003e(dental caries) AND (rs731236)\u003c/p\u003e \u003cp\u003e(dental caries) AND (rs1544410)\u003c/p\u003e \u003cp\u003e(dental caries) AND (CdX2)\u003c/p\u003e \u003cp\u003e(dental caries) AND (FokI)\u003c/p\u003e \u003cp\u003e(dental caries) AND (ApaI)\u003c/p\u003e \u003cp\u003e(dental caries) AND (TaqI)\u003c/p\u003e \u003cp\u003e(dental caries) AND (BsmI)\u003c/p\u003e \u003cp\u003eLast update posted on or before 08/31/2022\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCNKI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(\u0026ldquo;龋齿\u0026rdquo;or\u0026ldquo;龋病\u0026rdquo;) and (维生素D受体) and (多态性)\u003c/p\u003e \u003cp\u003e(\u0026ldquo;龋齿\u0026rdquo;or\u0026ldquo;龋病\u0026rdquo;) and (\u0026ldquo;TaqI\u0026rdquo;or \u0026ldquo;ApaI\u0026rdquo;or\u0026ldquo;FokI\u0026rdquo;or\u0026ldquo;BsmI\u0026rdquo;or \u0026ldquo;CdX2\u0026rdquo;)\u003c/p\u003e \u003cp\u003e(\u0026ldquo;龋齿\u0026rdquo;or\u0026ldquo;龋病\u0026rdquo;) and (\u0026ldquo;rs10735810\u0026rdquo;or\u0026ldquo;rs731236\u0026rdquo;or\u0026ldquo;rs1544410\u0026rdquo;\u003c/p\u003e \u003cp\u003eor\u0026ldquo;rs7975232\u0026rdquo;or\u0026ldquo;rs11568820\u0026rdquo;)\u003c/p\u003e \u003cp\u003e截止日期: 2022年8月31日\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWanfang\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(龋齿)(维生素D受体) (多态性)\u003c/p\u003e \u003cp\u003e(龋)(TaqI) + (龋)(ApaI) + (龋)(FokI) + (龋)(BsmI) + (龋)(CdX2)\u003c/p\u003e \u003cp\u003e(龋)(rs10735810) + (龋)(rs731236) + (龋)(rs1544410) + (龋)(rs7975232) + (龋)(rs11568820)\u003c/p\u003e \u003cp\u003e截止日期: 2022年8月31日\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCqvip\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(龋齿)(维生素D受体) (多态性)\u003c/p\u003e \u003cp\u003e(龋)(TaqI) + (龋)(ApaI) + (龋)(FokI) + (龋)(BsmI) + (龋)(CdX2) (龋)(rs10735810) + (龋)(rs731236) + (龋)(rs1544410) + (龋)(rs7975232) + (龋)(rs11568820)\u003c/p\u003e \u003cp\u003e截止日期: 2022年8月31日\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData extraction\u003c/h2\u003e \u003cp\u003eRelevant data were independently extracted from the included papers by two authors (XR Qin and Y Xu) in duplicate. Data extracted from the selected studies included study information (author, year, country, ethnicity, and study design), patient information (age, sample size, dentition type, and genotyping method), diagnostic information (diagnostic criteria for dental caries), and outcome information (VDR gene locus SNP loci and allele or genotype frequencies). To dichotomize the results of caries detection, the WHO 1997\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e, WHO 2013\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, and ICDAS II\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e caries diagnostic criteria were combined to determine caries and caries-free classifications, where individuals classified as ICDAS\u0026thinsp;=\u0026thinsp;0\u0026ndash;2 and DMFT\u0026thinsp;=\u0026thinsp;0 in WHO 1997 and WHO 2013 were considered the caries-free group, and those defined as ICDAS\u0026thinsp;=\u0026thinsp;3\u0026ndash;6 and DMFT\u0026thinsp;\u0026gt;\u0026thinsp;0 in WHO 1997 and WHO 2013 considered the caries group. In the included articles, PCR-restriction fragment length polymorphism (RFLP) and real-time quantitative PCR were used to detect genotypes; polymorphisms detected by PCR-RFLP were named according to restriction endonuclease binding sites, while those identified by real-time quantitative PCR were named according to alleles at the polymorphic site. For convenience, the one-to-one correspondence between genotypes named using the two methods with minor allele frequency was determined (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e) and variables are hereafter referred to using their unique reference SNP identification numbers.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eVDR SNP genotypes according to detection by the PCR-RFLP and real-time quantitative PCR detection method\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSNP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRestriction endonuclease/transcription factor binding site(s)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAllele\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePCR-RFLP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReal-time quantitative PCR\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ers731236\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTaqI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT/C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTt\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTC\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ett\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCC\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ers739837\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTaqI/BglI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eC/T\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ers10735810\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFokI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCC\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFf\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCT\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eff\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ers2228570\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFokI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA\u0026thinsp;\u0026gt;\u0026thinsp;G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ers7975232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eApaI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAC\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCC\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ers11568820\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCDX2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ers1544410\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBsmI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eA/G\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ebb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGG\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eQuality assessment\u003c/h2\u003e \u003cp\u003eQuality assessment of included studies was carried out independently by two authors (XR Qin and Y Xu), and any disagreements were resolved by consensus. As included studies were all observational (nonrandomized), an accurate assessment of bias risk could not be conducted, and hence only quality was assessed. The Newcastle Ottawa scale (NOS), with minor modification, was used to assess the quality of the studies (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ohri.ca//programs/clinical_epidemiology/oxford.asp\u003c/span\u003e\u003cspan address=\"https://www.ohri.ca//programs/clinical_epidemiology/oxford.asp\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e), and added conformed to Hardy-Weinberg equilibrium. The NOS evaluates the methodological quality of each study, following a star system based on nine domains grouped into four main sets, namely, patient selection, comparability of study groups, outcome assessment, and Hardy-Weinberg equilibrium, and is scored by awarding a point for each answer. Studies were categorized as high quality, moderate quality, and low quality if they reached 7\u0026ndash;9, 4\u0026ndash;6, or 0\u0026ndash;4 points, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eQuality assessment according to the Newcastle Ottawa scale\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eItem\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eScore criteria\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefinition of caries\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea. Yes, the definition and diagnosis of caries are correct, independent, and valid ☆\u003c/p\u003e \u003cp\u003eb. Yes, such as according to medical records or the doctor\u0026rsquo;s own records ☆\u003c/p\u003e \u003cp\u003ec. No description\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDisease representative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.Are consecutive cases, or cases are well represented ☆\u003c/p\u003e \u003cp\u003eb. Presence of selectivity bias or no description\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDefinition of the caries-free group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.No history of caries; patients to be studied☆\u003c/p\u003e \u003cp\u003eb.No description\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSelection of the caries-free group\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.Community control ☆\u003c/p\u003e \u003cp\u003eb.Hospital control\u003c/p\u003e \u003cp\u003ec. No description\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComparability of cases and controls\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.Controls selected and analyzed based on presence or absence of caries ☆\u003c/p\u003e \u003cp\u003eb.Controls selected and analyzed based on other factors\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExposure investigation and assessment methods\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.Reliable records ☆\u003c/p\u003e \u003cp\u003eb.Blind interview ☆\u003c/p\u003e \u003cp\u003ec. Unblinded interview self-report or medical record only\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ed. No description\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eThe same investigation method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.Yes ☆\u003c/p\u003e \u003cp\u003eb.No\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNonresponse rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.The nonresponse rate was the same in both groups ☆\u003c/p\u003e \u003cp\u003eb.No nonresponse rate was described\u003c/p\u003e \u003cp\u003ec. Nonresponse rate was different, but no reason was stated\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eConformed to Hardy-Weinberg equilibrium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ea.Hardy-Weinberg equilibrium ☆\u003c/p\u003e \u003cp\u003eb.Hardy-Weinberg disequilibrium\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSPSS 22.0 software (SPSS, Inc., Chicago, IL, USA) was used to apply the Kappa test to evaluate agreement among reviewers in article identification, screening, data extraction, and quality.\u003c/p\u003e \u003cp\u003eMeta-analysis was performed when warranted by the quality and quantity of included studies. Associations between VDR polymorphisms and caries were assessed by calculating odds ratio (OR) with 95% confidence interval (CI) values, based on four genetic models: allelic, recessive, dominant, and overdominant. Heterogeneity was assessed using the I\u003csup\u003e2\u003c/sup\u003e statistic and Cochrane\u0026rsquo;s Q test, with I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026gt;\u0026thinsp;50% or P\u0026thinsp;\u0026lt;\u0026thinsp;0.10 on Cochrane\u0026rsquo;s Q test, indicating substantial heterogeneity\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Publication bias was evaluated by visual inspection of funnel plots\u003csup\u003e[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e, as well as by Egger\u0026rsquo;s and Begg\u0026rsquo;s tests. Sensitivity analyses (one study removed) were used to evaluate the stability of the results of analysis of data from included studies. Subgroup analyses, based on ethnicity, genotyping method, and tooth dentition, were conducted to determine the effects of subgroups on the overall results, if sufficient articles were included. Forest plots, subgroup analysis, and publication bias were conducted using Review manager 5 software (Revman5.4), while sensitivity analyses, Egger\u0026rsquo;s test, and Begg\u0026rsquo;s test were performed using Comprehensive Meta-Analysis version 3.0 (CMA 3.0) software.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eSystematic search\u003c/h2\u003e\n \u003cp\u003eThe primary search identified 79 published papers, of which 14 satisfied the initial inclusion criteria. Reading of complete texts resulted in the inclusion of ten studies, of which nine were case-control studies\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e and one was a cross-sectional investigation\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e; four studies were excluded because the subjects were older than 18 years\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e(Table \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). Details of the process for selection of research articles are presented as a flow diagram in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003cp\u003eSeven SNPs were involved in the selected studies: rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820 (Tables\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). Six studies reported data on rs731236\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e, with 960 and 626 cases in the combined caries and control groups, respectively. Three studies reported data on rs739837\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e],\u003c/sup\u003e with 461 and 335 cases in the respective combined caries and control groups. The rs10735810 SNP was included in three studies\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, with 753 and 576 cases in the combined caries and control groups, respectively, and there were three studies on rs2228570\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e, with 492 and 363 combined case and control group subjects, respectively. The rs7975232 locus was included in three studies\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, with 752 cases in the combined caries group and 575 cases in the combined control group. There were four studies of rs1544410\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e, with 1065 and 676 cases in the combined caries and controls groups, respectively. Finally, rs11568820 was included in one study\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e, with 303 cases in the caries group and 245 cases in the control group .\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBasic characteristics of included articals\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAuthor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEthnicity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy design\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e(years)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDentition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample size\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGenotyping method\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSNPs\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDiagnostic criteria for caries\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNOS\u003c/p\u003e\n \u003cp\u003escore\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhang(2006)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.06\u003c/p\u003e\n \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 312\u003c/p\u003e\n \u003cp\u003eControl: 100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers1544410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQin( 2019)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 304\u003c/p\u003e\n \u003cp\u003eControl: 245\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReal-Time PCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers1544410\u003c/p\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003cp\u003ers7975232\u003c/p\u003e\n \u003cp\u003ers10735810\u003c/p\u003e\n \u003cp\u003ers11568820\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYu(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 200\u003c/p\u003e\n \u003cp\u003eControl: 200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers1544410\u003c/p\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003cp\u003ers7975232\u003c/p\u003e\n \u003cp\u003ers10735810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKong(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u0026ndash;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 249\u003c/p\u003e\n \u003cp\u003eControl: 131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers1544410\u003c/p\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003cp\u003ers7975232\u003c/p\u003e\n \u003cp\u003ers10735810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHolla(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCzech\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u0026ndash;15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 235\u003c/p\u003e\n \u003cp\u003eControl: 153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReal-Time PCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCogulu(2016)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTurkey\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u0026ndash;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 112\u003c/p\u003e\n \u003cp\u003eControl: 38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers7975232\u003c/p\u003e\n \u003cp\u003ers10735810\u003c/p\u003e\n \u003cp\u003ers11568820\u003c/p\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e(continued). Basic characteristics of included artical\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eFatturi (2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ecross-sectional\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCase: 208\u003c/p\u003e\n \u003cp\u003eControl:132\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eReal-Time PCR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ers739837\u003c/p\u003e\n \u003cp\u003ers2228570\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eWHO2013\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAribam(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u0026ndash;12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 235\u003c/p\u003e\n \u003cp\u003eControl: 153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO1997\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBarbosa(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u0026ndash;11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 203\u003c/p\u003e\n \u003cp\u003eControl: 150\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReal-Time PCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers2228570\u003c/p\u003e\n \u003cp\u003ers739837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICDAS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMadalen(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase-control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u0026ndash;13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCase: 138\u003c/p\u003e\n \u003cp\u003eControl: 19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReal-Time PCR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers2228570\u003c/p\u003e\n \u003cp\u003ers739837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWHO\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSummary of VDR gene SNP allele and genotype data\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSNP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAuthor(year)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"5\" align=\"left\"\u003e\n \u003cp\u003eCaries-group(DMFT\u0026thinsp;\u0026ge;\u0026thinsp;1)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"5\" align=\"left\"\u003e\n \u003cp\u003eCaries-free group(DMFT\u0026thinsp;=\u0026thinsp;0)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAribam(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQin(2019)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e449\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKong(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e479\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e251\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYu(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e171\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e371\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e358\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHolla(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e170\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCogulu(2016)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ers739837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eFatturi(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e101\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e199\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e112\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBarbosa(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e167\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e222\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e182\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMadalena(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ers10735810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eQin(2019)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eT\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e221\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYu(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e268\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e184\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKong(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e132\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e228\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e131\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ers2228570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eFatturi(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e279\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBarbosa(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e264\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMadalena(2020)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab8\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e(continued). Summary of VDR gene SNP allele and genotype data\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSNP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAuthor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"5\" align=\"left\"\u003e\n \u003cp\u003eCaries-group(DMFT\u0026thinsp;\u0026ge;\u0026thinsp;1)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"3\" align=\"left\"\u003e\n \u003cp\u003eCaries-free group(DMFT\u0026thinsp;=\u0026thinsp;0)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth colspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ers1544410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eQin(2019)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e580\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e457\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYu(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e364\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e369\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKong(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e152\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e202\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhang(2006)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e106\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e190\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ers7975232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003eQin(2019)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e443\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e163\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e123\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYu(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e273\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eKong(2017)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e323\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e175\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e183\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ers11568820\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eQin(2019)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e198\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e145\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e343\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"12\"\u003eIn Cogulu\u0026rsquo;s study\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e, FokI, ApaI and CDX2 had no significant difference between the case group and the control group, and the specific data of each genotype was not mentioned.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eQuality assessment and Kappa test\u003c/h2\u003e\n \u003cp\u003eQuality assessment of the included studies is shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Overall, six studies were considered high quality\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e, and four were moderate quality\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e; none was low quality (Tables\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe Kappa coefficients of the reviewers involved in article identification and screening, data extraction, and quality assessment were 0.892, 0.893, and 1.000 (Table S2); hence, all had values of \u0026gt;\u0026thinsp;0.800, indicating strong agreement among reviewers\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch2\u003eMeta-analysis\u003c/h2\u003e\n\u003cp\u003eThe rs11568820 locus was only included in one article\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e and was, therefore, not subjected to meta-analysis. The other six loci included in this study, namely, rs731236, rs739837, rs10735810, rs2228570, rs7975232, and rs1544410, were analyzed by meta-analysis. Subgroup analyses of rs731236 were also conducted, according to genotype detection method, ethnicity, and tooth dentition (primary, mixed, and permanent).\u003c/p\u003e\n\u003cp\u003eThe distribution of rs731236 T and C alleles did not differ significantly between subjects with and without caries (OR\u0026thinsp;=\u0026thinsp;1.01, 95% CI: 0.83\u0026ndash;1.21, P\u0026thinsp;=\u0026thinsp;0.96); however, analysis under the overdominant genetic model showed that distribution of TT, TC, and CC genotypes differed significantly between subjects with and without caries, with the caries risk of the population with homozygous (TT or CC) genotypes 1.33-fold higher than that of the population with the heterozygous (TC) genotype (OR\u0026thinsp;=\u0026thinsp;1.33, 95% CI: 1.06\u0026ndash;1.67, P\u0026thinsp;=\u0026thinsp;0.02). Heterogeneity testing indicated no significant heterogeneity among the studies (I\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0%, P\u0026thinsp;=\u0026thinsp;0.51). Further, sensitivity analysis showed that the combined effect magnitude did not change significantly after removal of any study, indicating that the results were reliable(Fig \u003cspan class=\"InternalRef\"\u003eS1\u003c/span\u003e). Further, funnel plot, Egger\u0026rsquo;s test, and Begg\u0026rsquo;s tests revealed no evidence of publication bias in the included literature (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab9\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eResults of meta-analysis of VDR SNPs alleles under different genetic models\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSNP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEffect model\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eZ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eI2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBegg\u003c/p\u003e\n \u003cp\u003etest\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEgger\u003c/p\u003e\n \u003cp\u003etest\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity test\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" align=\"left\"\u003e\n \u003cp\u003ers731236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllele(T VS.C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.01 (0.83\u0026ndash;1.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(TT VS. TC\u0026thinsp;+\u0026thinsp;CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04(0.98,1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant(TT\u0026thinsp;+\u0026thinsp;TC VS. CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75(0.54,1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverdominant(TT\u0026thinsp;+\u0026thinsp;CC VS. TC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33(1.06,1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" align=\"left\"\u003e\n \u003cp\u003ers739837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllele(T VS.C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00(0.81,1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(TT VS. TG\u0026thinsp;+\u0026thinsp;GG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93(0.68,1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant(TT\u0026thinsp;+\u0026thinsp;TG VS. GG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.09(0.76,1.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverdominant(TT\u0026thinsp;+\u0026thinsp;GG VS. TG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89(0.66,1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" align=\"left\"\u003e\n \u003cp\u003ers10735810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllele(C VS. T)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33(1.30, 2.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(CC VS. CT\u0026thinsp;+\u0026thinsp;TT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.23(1.04,2.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant(CC\u0026thinsp;+\u0026thinsp;CT VS. TT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.87(1.15,3.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOver-dominant(CC\u0026thinsp;+\u0026thinsp;TT VS. CT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.83(0.67,1.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\n \u003cp\u003ers2228570\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllele(A VS.G)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07(0.70,1.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(AA VS. AG\u0026thinsp;+\u0026thinsp;GG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.09(0.70,1.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant(AA\u0026thinsp;+\u0026thinsp;AG VS. GG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.07(0.59,1.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverdominant(AA\u0026thinsp;+\u0026thinsp;GG VS. AG)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.04(0.64,1.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab10\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003e(continued). Results of meta-analysis of VDR SNPs alleles under different genetic models\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSNP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEffect model\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eZ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eI2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eBegg\u003c/p\u003e\n \u003cp\u003etest\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEgger\u003c/p\u003e\n \u003cp\u003etest\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSensitivity test\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" align=\"left\"\u003e\n \u003cp\u003ers7975232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllele(C VS. A)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.89(0.70,1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(CC VS. CA\u0026thinsp;+\u0026thinsp;AA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.87(0.70,1.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant(CC\u0026thinsp;+\u0026thinsp;CA VS. AA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.91(0.55,1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverdominant(CC\u0026thinsp;+\u0026thinsp;AA VS. CA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.91(0.73,1.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" align=\"left\"\u003e\n \u003cp\u003ers1544410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllele(G VS. A)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.56(0.76,3.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(GG VS. GA\u0026thinsp;+\u0026thinsp;AA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58(0.26,1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e89%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(GG VS. GA\u0026thinsp;+\u0026thinsp;AA)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86(0.48,1.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverdominant(AA\u0026thinsp;+\u0026thinsp;GG VS. GA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60(0.28,1.25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eyes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverdominant(AA\u0026thinsp;+\u0026thinsp;GG VS. GA)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45(0.48,1.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eno\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"11\"\u003e*Removed study of Zhang(2006)\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eSubgroup analysis of rs731236 demonstrated that caries risk was higher in subjects with homozygous (TT or CC) genotype, permanent dentition, and Asian ethnicity, genotyped by real-time quantitative PCR, than in those with heterozygous (TC) genotype, permanent dentition (OR\u0026thinsp;=\u0026thinsp;1.48, 95% CI: 1.07\u0026ndash;2.03, P\u0026thinsp;=\u0026thinsp;0.02), and Asian ethnicity (OR\u0026thinsp;=\u0026thinsp;1.38, 95% CI: 1.02\u0026ndash;1.87, P\u0026thinsp;=\u0026thinsp;0.03), genotyped by real-time quantitative PCR (OR\u0026thinsp;=\u0026thinsp;1.52, 95% CI: 1.10\u0026ndash;210, P\u0026thinsp;=\u0026thinsp;0.01) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab13\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSubgroup meta-analysis of rs731236 alleles under different genetic models, according to dentition type\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDentition\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEffect model\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eZ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eI2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" align=\"left\"\u003e\n \u003cp\u003eAllele(T VS.C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98(0.76\u0026ndash;1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.45(0.96\u0026ndash;2.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80(0.55\u0026ndash;1.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90(0.54\u0026ndash;1.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" align=\"left\"\u003e\n \u003cp\u003eRecessive(TT VS. TC\u0026thinsp;+\u0026thinsp;CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.21(0.93\u0026ndash;1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.49(0.97\u0026ndash;2.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.73(0.43\u0026ndash;1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.36(0.89\u0026ndash;2.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" align=\"left\"\u003e\n \u003cp\u003eDominant(TT\u0026thinsp;+\u0026thinsp;TC VS. CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75(0.54\u0026ndash;1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.25(0.08\u0026ndash;20.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81(0.44\u0026ndash;1.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72(0.48\u0026ndash;1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" align=\"left\"\u003e\n \u003cp\u003eOver-dominant(TT\u0026thinsp;+\u0026thinsp;CC VS. TC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33(1.06\u0026ndash;1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrimary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.49(0.97\u0026ndash;2.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.85(0.50\u0026ndash;1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePermanent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.48(1.07\u0026ndash;2.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable id=\"Tab14\" border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSubgroup meta-analysis of rs731236 alleles under different genetic models, according to ethnicity\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEthnicity\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEffect model\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eZ\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eI2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAllele(T VS.C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003erandom\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98(0.76\u0026ndash;1.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.98(0.65\u0026ndash;1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00(0.72\u0026ndash;1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRecessive(TT VS. TC\u0026thinsp;+\u0026thinsp;CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.21(0.93\u0026ndash;1.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.16(0.85\u0026ndash;1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.05(0.56\u0026ndash;1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant(TT\u0026thinsp;+\u0026thinsp;TC VS. CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.75(0.54\u0026ndash;1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.69(0.44\u0026ndash;1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.84(0.50\u0026ndash;1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOver-dominant(TT\u0026thinsp;+\u0026thinsp;CC VS. T)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.33(1.06\u0026ndash;1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAsian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.38(1.02\u0026ndash;1.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCaucasian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.26(0.88\u0026ndash;1.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable border=\"1\"\u003e\n \u003ccaption\u003e\n \u003cp\u003eTable 9\u003c/p\u003e\n \u003cp\u003eSubgroup meta-analysis of rs731236 alleles under different genetic models, according to genotype detection method\u003c/p\u003e\n \u003c/caption\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003eGenotyping method\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003eEffect model\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003eOR（95%CI）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003eZ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003eI2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21%\"\u003e\n \u003cp\u003eAllele (T VS.C)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e1.01(0.83-1.21）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e41%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"21%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"16%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e0.79(0.60-1.04）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17%\"\u003eReal-Time PCR\u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e1.24(0.96-1.60）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e1.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e36%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21%\"\u003e\n \u003cp\u003eRecessive(TT VS. TC+CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e1.21(0.93-1.56）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e27%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"21%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"16%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e1.49(0.97-2.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e1.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17%\"\u003eReal-Time PCR\u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e0.83(0.54-1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21%\"\u003e\n \u003cp\u003eDominant(TT+TC VS. CC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e0.75（0.54-1.05）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"21%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"16%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e0.70(0.47-1.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e1.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17%\"\u003eReal-Time PCR\u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e0.87(0.47-1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21%\"\u003e\n \u003cp\u003eOver-dominant(TT+CC VS. TC)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16%\"\u003e\n \u003cp\u003efixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e1.33(1.06-1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e2.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" width=\"21%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\"\u003e\n \u003cp\u003ePCR-RFLP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" width=\"16%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e1.15(0.83-1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e0.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17%\"\u003eReal-Time PCR\u003c/td\u003e\n \u003ctd width=\"11%\"\u003e\n \u003cp\u003e1.52(1.10-2.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8%\"\u003e\n \u003cp\u003e2.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6%\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10%\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFunnel plot indicated that there was significant heterogeneity between the study by Yu et al.\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e and the other two included articles that analyzed rs10735810 SNP data; however, Begg\u0026rsquo;s (Z\u0026thinsp;=\u0026thinsp;1.04, P\u0026thinsp;=\u0026thinsp;0.30) and Egger\u0026rsquo;s (t\u0026thinsp;=\u0026thinsp;1.83, P\u0026thinsp;=\u0026thinsp;0.32) tests indicated that there was no publication bias in these articles; therefore, a random effects model was used to merge the quantitative effects reported by the studies (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb and \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). The distribution of rs10735810 C and T alleles differed significantly between subjects with and without caries (OR\u0026thinsp;=\u0026thinsp;1.33, 95% CI: 1.30\u0026ndash;2.30, P\u0026thinsp;=\u0026thinsp;0.03). Subjects with the CC\u0026thinsp;+\u0026thinsp;CT genotype had a significant 1.87-fold higher risk of caries than those with the TT genotype (OR\u0026thinsp;=\u0026thinsp;1.87, 95% CI: 1.15\u0026ndash;3.04, P\u0026thinsp;=\u0026thinsp;0.01).\u003c/p\u003e\n\u003cp\u003eThe detection rate of the rs1544410 AA genotype in the population was low. Analysis under the recessive and overdominant models showed that there were no significant differences in the proportions of GG or GA genotypes between children with and without caries (recessive model: OR\u0026thinsp;=\u0026thinsp;0.86, 95% CI: 0.48\u0026ndash;1.54, P\u0026thinsp;=\u0026thinsp;0.61; overdominant model: OR\u0026thinsp;=\u0026thinsp;0.45, 95% CI: 0.48\u0026ndash;1.49, P\u0026thinsp;=\u0026thinsp;0.56); however, there was substantial heterogeneity among the included articles. Moreover, sensitivity analysis demonstrated that the combined effect magnitude was significantly altered by excluding data from either of the articles, Qin\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e or Zhang\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e (Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e; Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ec and \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e; Fig S3).\u003c/p\u003e\n\u003cp\u003eMeta-analysis of the rs739837, rs2228570, and rs7975232 loci under recessive, dominant, and overdominant models demonstrated no significant differences in genotype distribution between the caries and noncaries groups (Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e;Fig.S4-S12).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis meta-analysis evaluated the relationship between VDR gene polymorphisms, including rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820, and risk of caries in subjects\u0026thinsp;\u0026lt;\u0026thinsp;18 years old.\u003c/p\u003e \u003cp\u003eWe found that homozygous (TT or CC) genotype at the rs731236 locus was associated with a 1.33-fold higher risk of caries than the heterozygous (TC) genotype (OR\u0026thinsp;=\u0026thinsp;1.33, 95% CI 1.06\u0026ndash;1.67, P\u0026thinsp;=\u0026thinsp;0.02), which differs from the findings of Lei et al.\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e In Lei\u0026rsquo;s study, rs731236 polymorphism with dental caries in the allele contrast model (C vs. T) and in the recessive genetic model (CC vs. TT/CT). This may be because, in our study, the subjects included were all \u0026le;\u0026thinsp;18 years old, and the oral environment, dietary habits, and microbial flora of adolescents differ from those in middle-aged and older adults\u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e, who were also included in the study by Lei et al. Moreover, basal and induced VDR expression can be regulated by environmental, genetic, and epigenetic factors\u003csup\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e, which may account for the observed differences in research results. Sadeghi et al.\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e found no significant difference in rs731236 between the two groups under an allelic model (T vs. C), similar to the findings of our study; however, under other genetic models, they also found no statistical difference between the two groups, which may be related to differences in meta-analysis effect models. Here, a fixed effect model was selected, according to the results of heterogeneity testing, while Sadeghi et al. used random effect models to analyze all inheritance models.\u003c/p\u003e \u003cp\u003eSubgroup analysis of rs731236 among different ethnic groups found that homozygous (TT or CC) genotype was associated with a higher risk of caries than heterozygous (TC) genotype (OR\u0026thinsp;=\u0026thinsp;1.38, 95% CI: 1.02\u0026ndash;1.87, P\u0026thinsp;=\u0026thinsp;0.03) under the overdominant genetic model in Asian populations, suggesting that homozygosity for this variant may be associated with caries risk in Asian populations, while no such correlation was found in the Caucasian population, consistent with the findings of Lei et al.\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e. These results may reflect regional and ethnic differences in the susceptibility to caries related to the rs731236 gene polymorphism.\u003c/p\u003e \u003cp\u003eBayram et al.\u003csup\u003e[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]\u003c/sup\u003e and Borilova et al.\u003csup\u003e[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/sup\u003e showed that genetic factors can have different effects on enamel caries in primary and permanent teeth. An insertion/deletion polymorphism in the gene encoding angiotensin converting enzyme may be related to permanent tooth caries but not to primary tooth caries, especially in women in the Czech population\u003csup\u003e[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]\u003c/sup\u003e. This study found similar results, in that the homozygous (TT or CC) genotype of rs731236 was associated with a higher risk of dental caries in permanent teeth than the heterozygous (TC) genotype under the overdominant genetic model (OR\u0026thinsp;=\u0026thinsp;1.48, 95% CI: 1.07\u0026ndash;2.03, P\u0026thinsp;=\u0026thinsp;0.02), similar to the findings of Lei et al.\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e, suggesting that genetic polymorphisms at the rs731236 locus are likely to affect the incidence of dental caries in permanent teeth but not in primary and mixed dentition.\u003c/p\u003e \u003cp\u003eAmong the ten reports included in our analysis, five\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e used the PCR-RFLP genotyping method, and five\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e used real-time quantitative PCR. The publication years of the PCR-RFLP studies were one in 2006\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e, one in 2016\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e, two in 2017\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e],\u003c/sup\u003e and one in 2020\u003csup\u003e[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/sup\u003e, while all literature reporting real-time quantitative PCR genotyping data was published since 2017, with three papers published in 2020\u003csup\u003e[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. Hence, the studies using real-time quantitative PCR genotyping were conducted more recently. This study found that, when using real-time quantitative PCR genotyping, the homozygous (TT or CC) genotype was associated with a higher risk of caries than the heterozygous (TC) genotype (OR\u0026thinsp;=\u0026thinsp;1.52, 95% CI: 1.10\u0026ndash;2.10, P\u0026thinsp;=\u0026thinsp;0.01) in the overdominant genetic model, which may reflect the comparatively higher specificity of real-time quantitative PCR genotyping, which uses a closed tube mode to detect the target gene during amplification, with no requirement for further downstream steps, such as gel electrophoresis, which can increase the specificity of detection and reduce the possibility of cross-contamination, suggesting that the results of analysis of the rs731236 polymorphism may be affected by different genotype detection methods.\u003c/p\u003e \u003cp\u003eResults of meta-analysis of rs10735810 allele and genotype data showed that C allele may be a risk factor for caries (OR\u0026thinsp;=\u0026thinsp;1.33, 95% CI: 1.30\u0026ndash;2.30, P\u0026thinsp;=\u0026thinsp;0.03), with the risk of caries in subjects carrying the C allele 1.87-fold higher than that in subjects without the C allele (OR\u0026thinsp;=\u0026thinsp;1.87, 95% CI: 1.15\u0026ndash;3.04, P\u0026thinsp;=\u0026thinsp;0.01). Sadeghi et al.\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e named genotypes at this locus based on restriction of endonuclease digestion sites. After one-to-one comparison, the results of this study were consistent with those of Sadeghi et al.\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e. The reason why rs10735810 is associated with susceptibility to caries may be related to the interaction of its cotranscription factors and its location in the gene structure\u003csup\u003e[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]\u003c/sup\u003e; rs10735810 is located near the 5'-untranslated region of the VDR gene, within the DNA binding domain\u003csup\u003e[\u003cspan additionalcitationids=\"CR48 CR49\" citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]\u003c/sup\u003e, and the polymorphism changes the first potential start codon of the VDR gene, from ATG to ACG, resulting in a VDR protein truncated by three amino acids, which is more effective in transactivation of vitamin D target genes\u003csup\u003e[\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]\u003c/sup\u003e. Although funnel plot analysis showed that there was heterogeneity between the findings of Yu et al.\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e and those of the other two included publications, Begg\u0026rsquo;s test (Z\u0026thinsp;=\u0026thinsp;1.04, P\u0026thinsp;=\u0026thinsp;0.30) and Egger\u0026rsquo;s test (t\u0026thinsp;=\u0026thinsp;1.83, P\u0026thinsp;=\u0026thinsp;0.32) indicated that there was no publication bias in these reports; our use of a random effects model to combine the effects can be expected to have mitigated the interference on the results of heterogeneity among the included studies to some extent.\u003c/p\u003e \u003cp\u003eThe rate of detection of the AA genotype at rs1544410 is low; three articles found no AA genotypes at this locus in the groups with caries\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, and there were also no individuals with this genotype in the group without caries in two studies\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e. The results of analysis under recessive and overdominant models showed that there were no significant differences in the proportions of GG or GA genotypes at rs1544410 between subjects with and without caries (OR\u0026thinsp;=\u0026thinsp;0.86, 95% CI: 0.48\u0026ndash;1.54, P\u0026thinsp;=\u0026thinsp;0.61; OR\u0026thinsp;=\u0026thinsp;0.45, 95%CI: 0.48\u0026ndash;1.49, P\u0026thinsp;=\u0026thinsp;0.56), suggesting that this locus may not be related to the risk of caries; however, studies including rs1544410 were highly heterogeneous. Sensitivity analysis found that if either of the studies by Qin et al.\u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e or Zhang et al.\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e were excluded, the magnitude of the combined effect changed significantly, but due to the limited number of articles included, more reliable results could not be obtained by eliminating articles. More new evidence is needed to further assess the correlation between the rs1544410 variant and the risk of caries.\u003c/p\u003e \u003cp\u003eThe results of meta-analysis of allelic, recessive, dominant, and overdominant models at rs739837, rs2228570, and rs7975232 revealed no significant differences in genotype distributions between the caries and caries-free groups, consistent with the findings of Sadeghi et al.\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e, suggesting that these polymorphisms are unlikely to be related to the risk of caries in children.\u003c/p\u003e \u003cp\u003eThe meta-analysis had several limitations. Firstly, the studies included in this study are mainly case-control studies. Some studies showed mismatched sample sizes between case and control groups, and these bias risks may not be avoided; Secondly, data on the SNP (rs11568820) were not subjected to meta-analysis because they were only reported in one article. Further research confirmation is needed from different races and regions. Finally, only one article studied linkage disequilibrium (LD) analysis\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. In this article, four SNPs (rs7975232, rs1544410, rs731236, rs10735810) showed strong evidence of recombination except for rs731236 and rs1544410 in caries group data. But the linkage of rs731236 and rs1544410 in caries group still did not reach a strong LD level. Despite the above limitations, this meta-analysis still has the following advantages: all study subjects met the Hardy-Weinbery equilibrium, the included studies involved a wide geographical distribution and different types of dentition, and all included studies had high quality scores. Therefore, this meta-analysis is a reasonable summary of the current published research findings and leads to more reliable conclusions.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe rs10735810 and rs731236 variants were related to caries risk, and the association of rs731236 with caries risk may be affected by dentition type, ethnicity, and genotype detection method. These findings imply that rs731236 has potential as an indicator of risk of caries in permanent dentition among Asian people, and that rs10735810 may also be an indicator of caries. The rs739837, rs2228570, and rs7975232 variants may not be associated with the risk of caries. Further, the evidence does not support an association of rs1544410 with risk of caries, but this finding requires further confirmation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVDR Vitamin D receptor\u003c/p\u003e\n\u003cp\u003eOR Odds ratios\u003c/p\u003e\n\u003cp\u003eCI confidence intervals\u003c/p\u003e\n\u003cp\u003eECC early childhood caries\u003c/p\u003e\n\u003cp\u003eSNP single nucleotide polymorphism\u003c/p\u003e\n\u003cp\u003eNOS The Newcastle Ottawa scale\u003c/p\u003e\n\u003cp\u003eLD linkage disequilibrium\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupported by Assistant Research Fund for the president of Jinan Stomatological Hospital (2019-05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy design: XR Qin, Y Xu and M Wang. Database searched, data extraction and data synthesis: XR Qin and M Wang. Initial manuscript draft: XR Qin, and M Wang. Critical revision of the manuscript: XR Qin, Y Xu, LL Wang and SJ Xiong. All authors read and approved the final version of the manuscript. XR Qin and M Wang contributed to the work equally.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank Dr Qingchun Yao for the work of this review of evidence.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBenjamin R M. Oral health: the silent epidemic[J]. Public Health Rep, 2010,125(2):158-159.\u003c/li\u003e\n\u003cli\u003ePetersen P E, Bourgeois D, Ogawa H, et al. The global burden of oral diseases and risks to oral health[J]. Bull World Health Organ, 2005,83(9):661-669.\u003c/li\u003e\n\u003cli\u003eDu MQ, Li Z, Jiang H, et al. Dental Caries Status and its Associated Factors among 3- to 5-year-old Children in China: A National Survey[J]. Chin J Dent Res, 2018,21(3):167-179.\u003c/li\u003e\n\u003cli\u003eSun H B, Zhang W, Zhou X B. Risk Factors associated with Early Childhood Caries[J]. Chin J Dent Res, 2017,20(2):97-104.\u003c/li\u003e\n\u003cli\u003eSheiham A. Dental caries affects body weight, growth and quality of life in pre-school children[J]. Br Dent J, 2006,201(10):625-626.\u003c/li\u003e\n\u003cli\u003eFinlayson T L, Siefert K, Ismail A I, et al. Psychosocial factors and early childhood caries among low-income African-American children in Detroit[J]. Community Dent Oral Epidemiol, 2007,35(6):439-448.\u003c/li\u003e\n\u003cli\u003eSelwitz R H, Ismail A I, Pitts N B. Dental caries[J]. Lancet, 2007,369(9555):51-59.\u003c/li\u003e\n\u003cli\u003eQin M, Li J, Zhang S, et al. Risk factors for severe early childhood caries in children younger than 4 years old in Beijing, China[J]. Pediatr Dent, 2008,30(2):122-128.\u003c/li\u003e\n\u003cli\u003eYildiz G, Ermis R B, Calapoglu N S, et al. Gene-environment Interactions in the Etiology of Dental Caries[J]. J Dent Res, 2016,95(1):74-79.\u003c/li\u003e\n\u003cli\u003eGustafsson B E, Quensel C E, Lanke L S, et al. The Vipeholm dental caries study; the effect of different levels of carbohydrate intake on caries activity in 436 individuals observed for five years[J]. Acta Odontol Scand, 1954,11(3-4):232-264.\u003c/li\u003e\n\u003cli\u003ePiekoszewska-Zietek P, Turska-Szybka A, Olczak-Kowalczyk D. Single Nucleotide Polymorphism in the Aetiology of Caries: Systematic Literature Review[J]. Caries Res, 2017,51(4):425-435.\u003c/li\u003e\n\u003cli\u003eBretz W A, Corby P M, Schork N J, et al. Longitudinal analysis of heritability for dental caries traits[J]. J Dent Res, 2005,84(11):1047-1051.\u003c/li\u003e\n\u003cli\u003eVieira A R, Modesto A, Marazita M L. Caries: review of human genetics research[J]. Caries Res, 2014,48(5):491-506.\u003c/li\u003e\n\u003cli\u003eBerdal A, Lezot F, Nefussi J R, et al. Mineralized dental tissues: a unique example of skeletal biodiversity derived from cephaic neural crest[J]. Morphologie, 2000,84(265):5-10.\u003c/li\u003e\n\u003cli\u003eValdivielso J M, Fernandez E. Vitamin D receptor polymorphisms and diseases[J]. Clin Chim Acta, 2006,371(1-2):1-12.\u003c/li\u003e\n\u003cli\u003eMesbah M, Nemere I, Papagerakis P, et al. Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization[J]. J Bone Miner Res, 2002,17(9):1588-1596.\u003c/li\u003e\n\u003cli\u003eSchroth R J, Jeal N S, Kliewer E, et al. The relationship between vitamin D and severe early childhood caries: a pilot study[J]. Int J Vitam Nutr Res, 2012,82(1):53-62.\u003c/li\u003e\n\u003cli\u003eTheodoratou E, Tzoulaki I, Zgaga L, et al. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials[J]. BMJ, 2014,348:g2035.\u003c/li\u003e\n\u003cli\u003eHujoel P P. Vitamin D and dental caries in controlled clinical trials: systematic review and meta-analysis[J]. Nutr Rev, 2013,71(2):88-97.\u003c/li\u003e\n\u003cli\u003eQin X, Shao L, Zhang L, et al. Investigation of Interaction between Vitamin D Receptor Gene Polymorphisms and Environmental Factors in Early Childhood Caries in Chinese Children[J]. Biomed Res Int, 2019,2019:4315839.\u003c/li\u003e\n\u003cli\u003eYu M, Jiang Q Z, Sun Z Y, et al. Association between Single Nucleotide Polymorphisms in Vitamin D Receptor Gene Polymorphisms and Permanent Tooth Caries Susceptibility to Permanent Tooth Caries in Chinese Adolescent[J]. Biomed Res Int, 2017,2017:4096316.\u003c/li\u003e\n\u003cli\u003eHu X P, Li Z Q, Zhou J Y, et al. Analysis of the association between polymorphisms in the vitamin D receptor (VDR) gene and dental caries in a Chinese population[J]. Genet Mol Res, 2015,14(3):11631-11638.\u003c/li\u003e\n\u003cli\u003eKong Y Y, Zheng J M, Zhang W J, et al. The relationship between vitamin D receptor gene polymorphism and deciduous tooth decay in Chinese children[J]. BMC Oral Health, 2017,17(1):111.\u003c/li\u003e\n\u003cli\u003eCogulu D, Onay H, Ozdemir Y, et al. The Role of Vitamin D Receptor Polymorphisms on Dental Caries[J]. J Clin Pediatr Dent, 2016,40(3):211-214.\u003c/li\u003e\n\u003cli\u003eIzakovicova H L, Borilova L P, Kastovsky J, et al. Vitamin D Receptor TaqI Gene Polymorphism and Dental Caries in Czech Children[J]. Caries Res, 2017,51(1):7-11.\u003c/li\u003e\n\u003cli\u003ePage M J, Mckenzie J E, Bossuyt P M, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews[J]. BMJ, 2021,372:n71.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization: Oral health surveys: basic methods[J]. Geneva: World Health Organization, 1997.\u003c/li\u003e\n\u003cli\u003eWorld Health Organization: Oral health surveys: basic methods[J]. Geneva: World Health Organization, 2013.\u003c/li\u003e\n\u003cli\u003eShoaib L, Deery C, Ricketts D N, et al. Validity and reproducibility of ICDAS II in primary teeth[J]. Caries Res, 2009,43(6):442-448.\u003c/li\u003e\n\u003cli\u003eSutton A J, Duval S J, Tweedie R L, et al. Empirical assessment of effect of publication bias on meta-analyses[J]. BMJ, 2000,320(7249):1574-1577.\u003c/li\u003e\n\u003cli\u003eZhang,L.,Sun L.W., Study on the relationship between caries and vitamin D receptor gene polymorphism in children in Changchun. ZHONGGUO FUYOU BAOJIAN, 2006(04): 541-543..\u003c/li\u003e\n\u003cli\u003eBarbosa M, Lima D C, Reis C, et al. Vitamin D receptor FokI and BglI genetic polymorphisms, dental caries, and gingivitis[J]. Int J Paediatr Dent, 2020,30(5):642-649.\u003c/li\u003e\n\u003cli\u003eAribam V G, Aswath N, Ramanathan A. Single-nucleotide polymorphism in Vitamin D receptor gene and its association with dental caries in children[J]. J Indian Soc Pedod Prev Dent, 2020,38(1):8-13.\u003c/li\u003e\n\u003cli\u003eMadalena I, Xavier T, Cruz G, et al. Evaluation of vitamin D receptor genetic polymorphisms with dental caries and developmental defects of enamel in Brazilian children.[J]. Pediatric Dental Journal, 2020,3(30):161-166.\u003c/li\u003e\n\u003cli\u003eFatturi A L, Menoncin B L, Reyes M T, et al. The relationship between molar incisor hypomineralization, dental caries, socioeconomic factors, and polymorphisms in the vitamin D receptor gene: a population-based study[J]. Clin Oral Investig, 2020,24(11):3971-3980.\u003c/li\u003e\n\u003cli\u003eLi Z.Q, et al., A study on the association of the gene polymorphisms of vitamin D receptor with dental caries susceptibility in Dongxiang and Bao\u0026apos;an minorities in Gansu province. Journal of Practical Stomatology, 2013. 29(4): 535-538.\u003c/li\u003e\n\u003cli\u003eNireeksha N, Hegde M N, Shetty S S, et al. FOK l Vitamin D Receptor Gene Polymorphism and Risk of Dental Caries: A Case-Control Study[J]. Int J Dent, 2022,2022:6601566.\u003c/li\u003e\n\u003cli\u003eProtyusha G B, Sundharam B S. Analysis of the association between polymorphisms in Vitamin D receptor gene and dental caries[J]. Indian J Dent Res, 2021,32(1):3-7.\u003c/li\u003e\n\u003cli\u003eLandis J R, Koch G G. The measurement of observer agreement for categorical data[J]. Biometrics, 1977,33(1):159-174.\u003c/li\u003e\n\u003cli\u003eLei W, Tian H, Xia Y. Association Between the TaqI (rs731236 T\u0026gt;C) Gene Polymorphism and Dental Caries Risk: A Meta-analysis[J]. Genet Test Mol Biomarkers, 2021,25(5):368-375.\u003c/li\u003e\n\u003cli\u003eBurcham Z M, Garneau N L, Comstock S S, et al. Patterns of Oral Microbiota Diversity in Adults and Children: A Crowdsourced Population Study[J]. Sci Rep, 2020,10(1):2133.\u003c/li\u003e\n\u003cli\u003eSaccone D, Asani F, Bornman L. Regulation of the vitamin D receptor gene by environment, genetics and epigenetics[J]. Gene, 2015,561(2):171-180.\u003c/li\u003e\n\u003cli\u003eSadeghi M, Golshah A, Godiny M, et al. The Most Common Vitamin D Receptor Polymorphisms (ApaI,FokI, TaqI, BsmI, and BglI) in Children with Dental Caries: A Systematic Review and Meta-Analysis[J]. Children (Basel), 2021,8(4).\u003c/li\u003e\n\u003cli\u003eBayram M, Deeley K, Reis M F, et al. Genetic influences on dental enamel that impact caries differ between the primary and permanent dentitions[J]. Eur J Oral Sci, 2015,123(5):327-334.\u003c/li\u003e\n\u003cli\u003eBorilova L P, Kastovsky J, Bartosova M, et al. ACE Insertion/Deletion Polymorphism Associated with Caries in Permanent but Not Primary Dentition in Czech Children[J]. Caries Res, 2016,50(2):89-96.\u003c/li\u003e\n\u003cli\u003eTanaka K, Miyake Y, Hanioka T, et al. VDR gene polymorphisms, interaction with smoking and risk of periodontal disease in Japanese women: the Kyushu Okinawa maternal and child health study[J]. Scand J Immunol, 2013,78(4):371-377.\u003c/li\u003e\n\u003cli\u003eKanan R M, Varanasi S S, Francis R M, et al. Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density in healthy male subjects[J]. Clin Endocrinol (Oxf), 2000,53(1):93-98.\u003c/li\u003e\n\u003cli\u003eIngles S A, Wang J, Coetzee G A, et al. Vitamin D receptor polymorphisms and risk of colorectal adenomas (United States)[J]. Cancer Causes Control, 2001,12(7):607-614.\u003c/li\u003e\n\u003cli\u003eChen H Y, Chen W C, Hsu C D, et al. Relation of vitamin D receptor FokI start codon polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal women in Taiwan[J]. Acta Obstet Gynecol Scand, 2002,81(2):93-98.\u003c/li\u003e\n\u003cli\u003eTworoger S S, Gates M A, Lee I M, et al. Polymorphisms in the vitamin D receptor and risk of ovarian cancer in four studies[J]. Cancer Res, 2009,69(5):1885-1891.\u003c/li\u003e\n\u003cli\u003eArai H, Miyamoto K, Taketani Y, et al. A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women[J]. J Bone Miner Res, 1997,12(6):915-921. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"early childhood caries (ECC), vitamin D receptor (VDR), single nucleotide polymorphism (SNP), gene polymorphisms, caries risk","lastPublishedDoi":"10.21203/rs.3.rs-4147261/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4147261/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eIn this study, we aimed to evaluate the association of Vitamin D receptor (VDR) gene polymorphisms with caries risk in children (\u0026lt;\u0026thinsp;18 years).\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe electronic databases PubMed, Cochrane, EMBASE, Web of Science, CNKI, Cqvip, and Wanfang were searched for observational studies on the relationship between VDR polymorphisms and caries, including cohort, case-control, and cross-sectional studies. Quality assessment of selected studies was conducted using the Newcastle Ottawa scale. Odds ratios (OR) with 95% confidence intervals (CI) values for associations of individual VDR polymorphisms with dental caries were calculated based on four genetic models: allelic, recessive, dominant, and overdominant. Of 79 studies considered, 10 (nine case-control and one cross-sectional) were selected for analysis; the studies involved seven VDR single nucleotide polymorphisms: rs731236, rs739837, rs10735810, rs2228570, rs7975232, rs1544410, and rs11568820.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e \u003cp\u003eAlleles C and T of rs10735810 were significantly differently distributed in the caries and caries-free groups (OR\u0026thinsp;=\u0026thinsp;1.33, 95% CI: 1.30\u0026ndash;2.30, P\u0026thinsp;=\u0026thinsp;0.03), with CC\u0026thinsp;+\u0026thinsp;CT genotypes at this locus associated with greater risk of developing caries than the TT genotype (OR\u0026thinsp;=\u0026thinsp;1.87, 95%CI: 1.15\u0026ndash;3.04, P\u0026thinsp;=\u0026thinsp;0.01). Further, TT\u0026thinsp;+\u0026thinsp;CC genotype at rs731236 was associated with a 1.33-fold higher risk of caries development than the TC genotype (OR\u0026thinsp;=\u0026thinsp;1.33, 95%CI:1.06\u0026ndash;1.67,P\u0026thinsp;=\u0026thinsp;0.02). On subgroup analysis, the association between rs731236 and caries risk was affected by dentition type, ethnicity, and genotyping method (permanent dentition: OR\u0026thinsp;=\u0026thinsp;1.48, 95%CI: 1.07\u0026ndash;2.03, P\u0026thinsp;=\u0026thinsp;0.02; Asian: OR\u0026thinsp;=\u0026thinsp;1.38, 95%CI: 1.02\u0026ndash;1.87, P\u0026thinsp;=\u0026thinsp;0.03; quantitative PCR test: OR\u0026thinsp;=\u0026thinsp;1.52, 95% CI: 1.10\u0026ndash;2.10, P\u0026thinsp;=\u0026thinsp;0.01). Genotype distributions at rs1544410, rs739837, rs2228570, and rs7975232 did not differ significantly between the caries and caries-free groups.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eCaries risk was associated with rs731236 and rs10735810 genotypes, and rs731236 may be a risk factor for permanent teeth caries among Asian people.\u003c/p\u003e","manuscriptTitle":"Association of Vitamin D Receptor Gene Polymorphisms with Caries Risk: A Systematic Review and Meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-01 17:08:06","doi":"10.21203/rs.3.rs-4147261/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-31T08:41:19+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-21T14:05:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-19T19:58:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-19T18:45:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"20962354661740230195748140938121319334","date":"2024-07-17T11:19:19+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-16T15:49:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"80358759649004845216459514848409874240","date":"2024-07-16T07:26:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184114561693439756768067866658298535182","date":"2024-07-10T13:22:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"83576127814263809583815439605705413790","date":"2024-07-10T11:24:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196059909649445016968963765296390763236","date":"2024-07-10T10:38:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-10T10:31:26+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-20T10:28:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-04-03T16:26:45+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-03T16:24:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2024-03-22T05:42:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c71f5341-4606-4d05-a8a9-f00f715ccbfa","owner":[],"postedDate":"April 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-10-14T16:07:56+00:00","versionOfRecord":{"articleIdentity":"rs-4147261","link":"https://doi.org/10.1186/s12887-024-05127-w","journal":{"identity":"bmc-pediatrics","isVorOnly":false,"title":"BMC Pediatrics"},"publishedOn":"2024-10-11 15:57:39","publishedOnDateReadable":"October 11th, 2024"},"versionCreatedAt":"2024-04-01 17:08:06","video":"","vorDoi":"10.1186/s12887-024-05127-w","vorDoiUrl":"https://doi.org/10.1186/s12887-024-05127-w","workflowStages":[]},"version":"v1","identity":"rs-4147261","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4147261","identity":"rs-4147261","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}