Effects of TMEM232 variant on blood lymphocyte counts in relation to incidence of infant atopic dermatitis

Effects of TMEM232 variant on blood lymphocyte counts in relation to incidence of infant atopic dermatitis | 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 Article Effects of TMEM232 variant on blood lymphocyte counts in relation to incidence of infant atopic dermatitis Eun-A Choi, Hee-Soo Han, Guemkyung Nah, So-Yeon Lee, Young-Youl Kim, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3312404/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Atopic dermatitis (AD) is caused by interactions between genetic susceptibility and environmental factors. Transmembrane protein 232 ( TMEM232 ) is one of the genes strongly implicated in AD. In the present study, we aimed to investigate the association between AD with variants within TMEM232 based on environmental factors, including feeding method. We performed a candidate gene association study involving the Cohort for Childhood Origins of Asthma and Allergic Diseases (infants, n = 1,054). A single variant of the TMEM232 gene, rs17132261, was found to be significantly associated with AD. Subjects carrying the wild-type allele (C) of rs17132261 had lower blood lymphocyte count than those carrying the variant rs17132261 (T). Multiple logistic regression analysis showed a statistically significant association between TMEM232 gene polymorphism and an increased risk of AD in one year old infants. Moreover, rs17132261 was associated with decreased blood lymphocyte counts in infants breastfed for six months. The group with the CC genotype showed lower lymphocyte counts than CT and TT carriers when breastfed. Our findings demonstrate that the TMEM232 risk allele, in combination with breastfeeding, lowers the number of lymphocytes, which could be a potential risk factor for AD. Biological sciences/Genetics Health sciences/Risk factors Figures Figure 1 Introduction Atopic Dermatitis (AD) is a multifactorial chronic disease characterized by skin inflammation caused by both genetic and environmental factors [1 2] . The prevalence of AD is the highest among children [3] . Global Burden of Disease data confirms that AD affects patients' quality of life and has a high global burden [4] . AD is a common inflammatory skin disease characterized by an imbalance between type 1 (Th1) and 2 (Th2) helper T cells [5] . During the progression of AD, IL-4 and IL-13, as central cytokines, promote Th2 differentiation by activating JAK-STAT signaling pathway [6] . In addition to the Th2-dominant immune responses seen in AD, immune cells such as B cells, dendritic cells, mast cells, and eosinophils also involve in the pathogenesis of AD by infiltrating lesions or secreting inflammatory mediators. [7] . Patients with AD have increased eosinophil counts and decreased lymphocyte counts in peripheral blood [8 9] . Studies have also reported that eosinophil-to-lymphocyte and neutrophil-to-lymphocyte ratios act as indicators for the improvement of clinical signs [10] and AD severity [11] in patients with AD. In addition, reduced lymphocyte counts, and elevated eosinophil and basophil counts have also been observed in patients with AD [9] . These studies suggest a relationship between the populations of immune cells and AD. Genome-wide association studies (GWAS) have identified 62 genes associated with AD, most of which encode skin barrier proteins involved in the innate and adaptive immune responses [12] . TMEM232 (transmembrane protein 232), located on chromosome 5q22.1, is strongly associated with AD [13–15] . Recently, haplotype analysis revealed that the H15 haplotype in the 5q22.1 region was associated with functional mutations in the TMEM232 gene [16] . TMEM232 has also been implicated in the development of several allergic diseases, the underlying mechanisms of which are thought to involve blood components. Additionally, some Asian populations, including Chinese and Japanese populations, are especially susceptible to allergic diseases owing to variations in TMEM232 [13 14] . However, an association between cord blood and the susceptibility to allergic diseases has not yet been reported in the Korean population. Here, we investigated the association between TMEM232 variant and blood parameters related to AD using Korean birth data and examined the potential relevance of TMEM232 variants in early childhood AD. Methods Study participants This study analyzed the Cohort for Childhood Origin of Asthma and Allergic Disease (COCOA), a prospective longitudinal study that aimed to investigate the effects of environmental and genetic factors on the development of allergic diseases. The COCOA study recruited 3,004 mothers from the general population before 26 weeks of gestation. [17] . Of these, 2,846 children were born, and regular follow-up visits for health and environmental questionnaires and physician examinations were conducted at 6 months, 1 year, and yearly thereafter. The participants who withdrew consent, had twins, missing blood counts, missing AD information, or missing genotype information were excluded. Ultimately, 1,054 infants were selected for this study (Fig. 1 ). This study was approved by the institutional review boards (IRBs) of Asan Medical Center (IRB no. 2008–0616 and 2015–1031), Samsung Medical Center (IRB no. 2009–02–021), Severance Hospital (IRB no. 4–2008 − 0588), CHA Medical Center (IRB no. 2010–010), and Seoul National University Hospital (IRB no. H-1401-086-550), and the Korea Disease Control and Prevention Agency (IRB no. 2020-03-06-C-A) and followed the guidelines of the Declaration of Helsinki (1975). Written informed consent was obtained from the parents of all the infants. Definition of atopic dermatitis AD in infants was evaluated through questionnaires at each scheduled visit, inquiring whether a physician had ever diagnosed AD and if so, whether interventions were prescribed for the condition. AD was defined according to criteria described by Hanifin and Rajka. The AD phenotype of the infants was considered at one year of age. A pediatric allergist assessed the SCORing Atopic Dermatitis (SCORAD) index [18] . Higher numbers indicate greater severity, and the scale ranges from 0 to 103. Measurement of leukocytes and IgE White blood cell counts and IgE levels (total IgE and milk-specific IgE) were measured. The percentage of blood leukocytes was calculated by using an automatic blood cell counter (XE-100; Sysmex Co., Kobe, Japan). Total serum IgE and milk-specific IgE levels were measured using a fluorescent enzyme immunoassay (AutoCAP System; Pharmacia Diagnostics AB, Uppsala, Sweden). Leukocyte and IgE levels in blood from infants at one-year-old were measured. Questionnaire data The questionnaire, which was based on the International Study of Asthma and Allergies in Childhood (ISAAC) was translated into Korean. The parents of the infants filled in a modified version of the questionnaire. The questionnaire consisted of (1) demographic factors, such as sex, date of birth, height, and weight; (2) symptom history related to AD; and (3) environmental factors related to allergic diseases, such as feeding method and residential patterns [19] . Genotyping DNA samples were genotyped using the Korea Biobank Array (KoreanChip) designed by the Korean National Institute of Health, Korea. The KoreanChip comprises 833,535 markers, including more than 247,000 rare frequencies or functional variants derived from the sequencing data of 2500 Koreans. Genotyping data were removed for low-quality SNPs with a low variant call rate (< 98%), excessive heterozygosity, and sex discrepancies [20] . For further studies, we selected candidate TMEM232 variants associated with AD. Statistical analysis All data are expressed as mean ± standard deviation (SDs) for continuous variables and as frequencies and proportions for categorical variables. To compare groups, t-tests and ANOVA were conducted for continuous variables, and the chi-square test was performed for categorical variables. Based on their TMEM232 genotype, we divided the participants into three groups. We performed logistic regression analysis to determine the relationship between TMEM232 rs17132261 genetic variants and AD, adjusted for maternal age, maternal drinking status, and breastfeeding. The association between blood lymphocyte levels and TMEM232 rs17132261 genetic variants based on breastfeeding status was determined using linear regression, adjusted for maternal age and drinking status. All p-values were two-tailed, and p-values below 0.05 were considered statistically significant. All statistical analyses were performed using R software (version 4.1.3). Results Characteristics of the study participants Participants’ characteristics are presented in Table 1 . A total of 269 infants were diagnosed with AD by doctors. Maternal lymphocytes were lower in infants with AD and showed significant differences according to the AD status of their offspring. The mean concentrations of total IgE and specific IgE to milk were 95.66 and 0.60 in the AD group, respectively, while 54.83 and 0.37 in the non-AD group, respectively. The mean eosinophils were 2.96 in the non-AD and 3.40 in the AD group, that is, the values were significantly different. In addition, the SCORAD index differed significantly between the two groups. TMEM232, a variant associated to AD, was also significantly associated with a higher risk of AD in the C allele. Table 1 Characteristics of mothers and one-year-old infants with atopic dermatitis Non-AD AD N Mean ± SD or % N Mean ± SD or % p-value Mother, n 785 269 WBC 676 8.99(± 2.95) 233 9.03(± 2.77) 0.857 Monocytes, % 540 6.81(± 1.95) 191 6.72(± 2.07) 0.579 Lymphocytes, % 542 21.24(± 8.84) 191 19.78(± 6.81) 0.039 Neutrophils, % 535 70.51(± 10.11) 187 71.8(± 8.44) 0.119 Eosinophils, % 539 1.15(± 1.15) 188 1.22(± 2.25) 0.618 Basophils, % 538 0.22(± 0.18) 188 0.20(± 0.16) 0.363 Total IgE 635 110.79(± 316.38) 212 103.62(± 288.45) 0.77 Der f-IgE 514 5.03(± 12.88) 156 5.81(± 15.72) 0.533 36w Der f 413 299.19(± 1082.45) 133 194.96(± 296.08) 0.273 Passive smoking 46 5.9 12 4.5 0.470 Pet ownership 235 30.4 78 29.3 0.810 Infant, n 785 269 WBC 782 8.88(± 2.50) 268 9.49(± 2.93) 0.001 Monocytes, % 785 8.02(± 2.96) 269 7.91(± 3.00) 0.593 Lymphocytes, % 785 62.76(± 10.53) 269 61.87(± 11.6) 0.247 Neutrophils, % 785 25.66(± 10.21) 267 26.04(± 10.63) 0.604 Eosinophils, % 785 2.96(± 1.91) 269 3.40(± 3.00) 0.005 Basophils, % 784 0.51(± 0.34) 269 0.55(± 0.48) 0.197 Total IgE 730 54.83(± 136.63) 239 95.66(± 227.98) 0.001 Milk IgE 730 0.37(± 0.99) 239 0.60(± 2.18) 0.023 SCORAD index 624 0.28(± 1.88) 203 8.04(± 9.92) < 0.001 TMEM232 0.002 CC 406 51.7 162 60.2 TC 308 39.2 99 36.8 TT 71 9.0 8 4.7 Values are presented as mean ± standard deviation. p-values are determined by t-test or chi-squared test. Parameters for the study participants according to TMEM232 genotype Table 2 lists the descriptive statistics for the study participants included in the analysis. The mean of lymphocytes at 1 year of age were 61.76, 63.49, and 63.17 in the CC, TC, and TT genotype, respectively, and there were significant differences among the three groups. The SCORAD index was the lowest in the case of TT genotype. There was a significant difference in the SCORAD index among the three groups. Table 2 Infants parameters by TMEM232 CC (n = 568) TC (n = 407) TT (n = 79) Number Mean ± SD or % Number Mean ± SD or % Number Mean ± SD or % p-value Biochemistry Total IgE 526 65.60 (± 174.25) 368 67.52 (± 164.74) 75 47.18 (± 68.8) 0.616 Milk-IgE 526 0.35 (± 0.92) 368 0.52 (± 1.75) 75 0.49 (± 1.91) 0.183 WBC 564 9.12 (± 2.57) 407 8.96 (± 2.70) 79 8.85 (± 2.67) 0.515 Monocytes, % 568 8.10 (± 2.95) 407 7.91 (± 2.93) 79 7.66 (± 3.27) 0.362 Lymphocytes, % 568 61.76 (± 11.48) 407 63.49 (± 9.81) 79 63.17 (± 10.53) 0.041 Neutrophils, % 568 26.38 (± 10.77) 405 24.95 (± 9.69) 79 25.43 (± 9.87) 0.100 Eosinophils, % 568 3.08 (± 2.17) 407 3.05 (± 2.41) 79 3.11 (± 1.94) 0.970 Basophils, % 568 0.53 (± 0.39) 406 0.52 (± 0.34) 79 0.50 (± 0.51) 0.826 SCORAD index 453 2.13 (± 6.02) 310 2.60 (± 6.77) 64 0.59 (± 2.98) 0.056 Feeding method 0.808 Breast feeding 131 56.2 85 36.5 17 7.3 Mixed feeding 376 52.6 282 39.4 57 7.9 Formula feeding 48 53.3 37 41.1 5 5.6 Association biochemistry parameters and feeding method Table 3 summarizes the descriptive statistics according to feeding method, which is an environmental indicator. The percentages of breast-feeding mixed feeding, and formula feeding were 22.45%, 68.88%, and 8.67%, respectively. Total IgE and milk-specific IgE levels were lower in breast-fed infants than in formula-fed infants. In addition, the mean lymphocyte count was lower in the breast-fed infants. Table 3 Infants biochemical parameters with respect to feeding method Breast feeding Mixed feeding Formula feeding Number Mean ± SD Number Mean ± SD Number Mean ± SD p-value Total IgE 206 69.57 (± 123.28) 665 68.70 (± 185.35) 84 27.85(± 48.18) 0.095 Milk-IgE 206 0.55 (± 1.95) 665 0.41 (± 1.25) 84 0.20 (± 0.46) 0.142 WBC 233 9.11 (± 2.77) 712 9.00 (± 2.62) 89 9.22 (± 2.46) 0.710 Monocytes, % 233 8.16 (± 3.15) 715 7.97 (± 2.90) 90 7.55 (± 2.99) 0.258 Lymphocytes, % 233 62.84 (± 10.42) 715 62.38 (± 11.08) 90 64.29 (± 9.04) 0.274 Neutrophils, % 233 25.23 (± 10.15) 713 25.91 (± 10.54) 90 24.84 (± 8.53) 0.499 Eosinophils, % 233 3.22 (± 2.78) 715 3.07 (± 2.12) 90 2.72 (± 1.61) 0.200 Basophils, % 233 0.52 (± 0.41) 714 0.53 (± 0.38) 90 0.53 (± 0.36) 0.981 Association between TMEM232 genotype and AD We analyzed the association between the genotype of TMEM232 variant rs173132261 and AD using logistic regression (Table 4 ). We found that infants with TC and CC genotype had a higher adjusted odds ratio (aOR) for the incidence of AD than infants with TT genotype (aOR 2.67; 95% CI 1.18–6.06; p-value = 0.018, aOR 3.55; 95% CI 1.59–7.96; p-value = 0.002). The incidence of AD was higher in individuals with the C allele than in those with the T allele. Table 4 Association between TMEM232 (rs17132261) and infant atopic dermatitis Genotype aOR 95% CI p-value TT Ref TC 2.67 1.18–6.06 0.018 CC 3.55 1.59–7.96 0.002 Adjusted for maternal age, maternal drinking status, feeding method Association between TMEM232 genotype and lymphocytes according to feeding method The association between lymphocytes and rs17132261 was assessed by dividing the infants into three groups according to feeding method (Table 5 ). We confirmed that breast-fed infants with the CC genotype had lower lymphocyte levels than those with the TT genotype, with mean lymphocyte levels of 61.98 for CC and 67.86 for TT. The mean lymphocyte levels were 64.22 and 56.82 for CC and TT, respectively, indicating that infants with the TT genotype had lower lymphocyte counts. In mixed-fed infants, there was no significant difference in lymphocytes according to the TMEM232 genotype. Table 5 Association between TMEM232 (rs17132261) and infant lymphocytes according to feeding method CC TC TT Mean ± SD p-value Mean ± SD p-value Mean ± SD p-value Breast feeding 61.98 (± 10.32) 0.025 63.15(± 10.76) 0.097 67.86 (± 8.23) Reference Mixed feeding 61.61 (± 11.89) 0.58 63.42(± 9.86) 0.6 62.33 (± 11.02) Reference Formula feeding 64.22 (± 10.54) 0.087 65.38(± 6.62) 0.04 56.82 (± 6.22) Reference Adjusted for maternal age, maternal drinking status Discussion AD is a multifactorial disease influenced by both genetic and environmental factors. The detection of AD in early life and the identification of genetic factors that interact with innocuous environmental factors are important for a timely diagnosis. In the present study, we identified TMEM232 as a candidate gene for AD in Korean infants by analyzing single-nucleotide polymorphisms reported in previous genome-wide studies on AD. Furthermore, we studied the association of TMEM232 genotypes and AD-associated phenotypes with decreased lymphocyte levels. We observed an association between the TMEM232 variant rs17132261 (C > T) in the cord blood and lymphocyte levels in infants with AD. Decreased lymphocyte levels are associated with an increased risk of developing AD in infants with the TMEM232 minor homozygous genotype (CC). These results indicate that the C allele of rs17132261 is a risk factor for infant AD and may manifest its effects through a decreased lymphocyte count. Previous studies suggested that TMEM232 is a potential genetic risk factor for AD. A GWAS conducted at the UK Biobank Europeans confirmed the association of TMEM232 with allergic diseases [21] , immunoglobulin type E in grass [22] , and AD [23 24] . Moreover, Japanese and Chinese Han GWAS have reported TMEM232 as a novel gene associated with AD [13 14] . Additionally, locus 5q22.1, which includes the AD-associated gene, TMEM232 , has been re-verified [23] and thoroughly sequenced in the Chinese population [16] . Genetic variants of TMEM232 are associated with several allergic diseases, including AD [22 25–27] . A study on European participants confirmed an association between TMEM232 and allergic rhinitis [22] . TMEM232 has been confirmed to be associated with childhood food allergies [25] and asthma [27] . However, a GWAS [28] and candidate-gene approach [29] in Korean children showed only a modest association between the four SNPs of TMEM232 , excluding rs13361382, and a potential association between SCORing AD values and TMEM232. In this study, we confirmed the association between AD and TMEM232 variant rs17132261, which is mediated by decreased lymphocyte levels in Korean infants. Transmembrane proteins (TMEM) are firmly attached to cellular membranes. TMEMs play crucial roles in cellular physiology, including transportation, signal transduction, and intercellular communication [30–32] . Although the specific functions of TMEM family proteins are still poorly characterized, new findings have highlighted the importance of the TMEM family as prognostic markers for various diseases [33–35] . Among TMEM family proteins, TMEM45A has been reported to be correlated with epidermal keratinization through the Golgi network in both in vivo and in vitro models [36] . TMEM79 is a predisposing gene for AD which is related to lamellar granule system, mast cell degranulation, and skin barrier function [7 37 38] . TMEM232 has also been identified as a susceptibility gene for AD according to several GWAS [13 14 16 24] , the molecular function of which has recently been investigated [39] . Han et al. reported that TMEM232 is overexpressed in skin tissues of AD patients and mice, and inflamed skin cells and promotes inflammatory responses via the nuclear factor-κB and STAT3 pathways, resulting in the formation of AD-like lesions [39] . Wu et al. reported the expression of TMEM232 in the granular layer and weak expression in the basal layer of skin samples from Chinese patients with AD using immunohistochemical staining [24] . No significant, positive expression of TMEM232 was found in the cytoplasm of lymphocytes around blood vessels [24] . Studies have shown that IL-10-producing B cells are decreased in AD patients, and IL-13-producing cells, which are supposed to be a type of lymphocyte, are also reduced in the breast milk of AD infants, suggesting an association between AD and lymphopenia [40 41] . Collectively, these studies suggested that TMEM232, a gene that regulates AD-related inflammation and lymphocytes, could be a target for AD treatment. TMEM232 and lymphocytes were confirmed to be related to AD as genetic factors, and a marginal correlation showed that breastfeeding increased the risk of AD as an environmental factor. Several studies have reported that the role of breastfeeding in AD is inconsistent and still controversial [42–50] . Recent studies reported that breastfeeding increases the incidence of AD [46–48] . A cohort study in Taiwan showed that breastfeeding may be a risk factor for AD [46] . Korean studies have reported that breastfeeding is not associated with or does not increase the risk of AD [47 48] . Other studies have shown that prolonged breastfeeding increases the risk of AD [49 50] . These results are consistent with our findings that breastfeeding is a potential risk factor for AD in infants. Our results suggest that TMEM232 interacts with breastfeeding to decrease lymphocyte levels, which affects the risk of AD. Some studies have shown that breastfeeding protects against AD [42 43] . These results conflict with our findings because we did not adjust for maternal lifestyle, socioeconomic status, or educational level. The present study is valuable because it is easy to translate the obtained results to the general population because we analyzed the disease phenotypes of infants in a natural birth cohort and not in a case-control study. In particular, this is the first study to confirm the association between the blood lymphocyte counts of infants, infant TMEM232 variants, and AD in the Korean population. In conclusion, this study reports that the TMEM232 gene of cord blood is associated with infant blood lymphocyte counts, which are important in mounting normal immune responses and allergic diseases. Moreover, TMEM232 variant rs17132261 may be implicated in the lymphocyte-mediated pathogenesis of AD and other allergic diseases. Determining the association between TMEM232 genotype and AD may provide insights into the biological mechanisms underlying AD in the Korean population. Declarations ACKNOWLEDGMENTS This study was supported by the Korea National Institute of Health (2020-NG-007-00, 2020-NG-007-01, 2020-NG-007-02, 2023-NI-008-00, 2017-E67002-00, 2017-E67002-01, 2017-E67002-02, 2020-E6702-00, and 2020-E6702-01) and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (2014R1A2A1A10050687). AUTHOR CONTRIBUTIONS All authors had full access to the data. H.-J.L. was responsible for the integrity of the data and the accuracy of data analysis. H.-J. L. conceived and designed the study. E.A.C. performed the statistical analyses, and H.-S. H. G. K. N., S.Y.L., and H.-J. L. interpreted the data. E.A.C., G. K. N., and H.-J.L. wrote the initial draft of the manuscript, and S. J. H., Y.Y.K., and H. J. L. reviewed and edited the manuscript. All authors have read and approved the final manuscript. DATA AVAILABILITY The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request. COMPETING INTERESTS The authors declare that there are no conflicts of interest. References Appiah, M. M. et al. Atopic dermatitisReview of comorbidities and therapeutics. Ann. Allergy Asthma Immunol. 129 , 142-149 (2022). Eichenfield, L. F. et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J. Am. Acad. Dermatol. 70 , 338-351 (2014). Silverberg, J. I. et al. Atopic dermatitis in the pediatric population: A cross-sectional, international epidemiologic study. Ann. Allergy Asthma Immunol. 126, 417–428.e2 (2021). Laughter, M. R. et al. The global burden of atopic dermatitis: Lessons from the Global Burden of Disease Study 1990-2017. Br. J. Dermatol. 184 , 304-309 (2021). Bieber, T. Atopic dermatitis. N. Engl. J. Med. 358 , 1483-1494 (2008). Huang, I. H., Chung, W. H., Wu, P. C. & Chen, C. B. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review. Front. Immunol. 13 , 1068260 (2022). Saunders, S. P. et al. Dysregulated skin barrier function in Tmem79 mutant mice promotes IL-17A-dependent spontaneous skin and lung inflammation. Allergy 75 , 3216-3227 (2020). Park, Y. M. & Bochner, B. S. Eosinophil survival and apoptosis in health and disease. Allergy Asthma Immunol. Res. 2 , 87-101 (2010). Zeng-Yun-Ou, Z., Zhong-Yu, J. & Wei, L. Bidirectional associations between eosinophils, basophils, and lymphocytes with atopic dermatitis: A multivariable Mendelian randomization study. Front. Immunol. 13 , 1001911 (2022). Hagino, T., Saeki, H., Fujimoto, E. & Kanda, N. The eosinophil-to-lymphocyte ratio acts as an indicator for improvement of clinical signs and itch by upadacitinib treatment in atopic dermatitis. J. Clin. Med. 12 (2023). Dogru, M. & Citli, R. The neutrophil-lymphocyte ratio in children with atopic dermatitis: A case-control study. Clin. Ter. 168 , e262-e265 (2017). Kader, H. A. et al. Current insights into immunology and novel therapeutics of atopic dermatitis. Cells 10 (2021). Hirota, T. et al. Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat. Genet. 44 , 1222-1226 (2012). Sun, L. D. et al. Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. Nat. Genet. 43 , 690-694 (2011). Tamari, M. & Hirota, T. Genome-wide association studies of atopic dermatitis. J. Dermatol. 41 , 213-220 (2014). Zheng, J. et al. Confirming the TMEM232 gene associated with atopic dermatitis through targeted capture sequencing. Sci. Rep. 11 , 21830 (2021). Yang, H. J. et al. The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: Design, rationale and methods. BMC Pulm. Med. 14 , 109 (2014). Severity scoring of atopic dermatitis: The SCORAD index. Consensus report of the European Task Force on Atopic Dermatitis. Dermatol. (Basel Switzerland) 186 , 23-31 (1993). Yang, S. I. et al. Effect of antibiotic use and mold exposure in infancy on allergic rhinitis in susceptible adolescents. Ann. Allergy Asthma Immunol. 113 , 160–165.e1 (2014). Moon, S. et al. The Korea biobank array: Design and identification of coding variants associated with blood biochemical traits. Sci. Rep. 9 , 1382 (2019). Zhu, Z. et al. Author Correction: A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases. Nat. Genet. 50 , 1753 (2018). Ramasamy, A. et al. A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. J. Allergy Clin. Immunol. 128 , 996-1005 (2011). Portelli, M. A., Hodge, E. & Sayers, I. Genetic risk factors for the development of allergic disease identified by genome-wide association. Clin. Exp. Allergy 45 , 21-31 (2015). Wu, Y. Y. et al. Scanning indels in the 5q22.1 region and identification of the TMEM232 susceptibility gene that is associated with atopic dermatitis in the Chinese Han population. Gene 617 , 17-23 (2017). Hirota, T. et al. Association study of childhood food allergy with genome-wide association studies-discovered loci of atopic dermatitis and eosinophilic esophagitis. J. Allergy Clin. Immunol. 140 , 1713-1716 (2017). Choi, B. Y., Han, M., Kwak, J. W. & Kim, T. H. Genetics and epigenetics in allergic rhinitis. Genes 12 (2021). Schoettler, N., Rodríguez, E., Weidinger, S. & Ober, C. Advances in asthma and allergic disease genetics: Is bigger always better? J. Allergy Clin. Immunol. 144 , 1495-1506 (2019). Kim, K. W. et al. Genome-wide association study of recalcitrant atopic dermatitis in Korean children. J. Allergy Clin. Immunol. 136 , 678–684.e4 (2015). Kim, J. H. et al. Association of genetic polymorphisms with atopic dermatitis, clinical severity and total IgE: A replication and extended study. Allergy Asthma Immunol. Res. 10 , 397-405 (2018). Zhang, N., Pan, H., Liang, X., Xie, J. & Han, W. The roles of transmembrane family proteins in the regulation of store-operated Ca2+ entry. Cell. Mol. Life Sci. 79 , 118 (2022). Chen, J. et al. TMEM196 inhibits lung cancer metastasis by regulating the Wnt/β-catenin signaling pathway. J. Cancer Res. Clin. Oncol. 149 , 653-667 (2023). Zhang, S. et al. TMEM116 is required for lung cancer cell motility and metastasis through PDK1 signaling pathway. Cell Death Dis. 12 , 1086 (2021). Zhang, L., Liu, S. Y., Yang, X., Wang, Y. Q. & Cheng, Y. X. TMEM206 is a potential prognostic marker of hepatocellular carcinoma. Oncol. Lett. 20 , 174 (2020). Deng, H. et al. High expression of TMEM200A is associated with a poor prognosis and immune infiltration in gastric cancer. Pathol. Oncol. Res. 29 , 1610893 (2023). Orphal, M. et al. TMEM63C, a Potential Novel Target for Albuminuria Development, Is Regulated by MicroRNA-564 and transforming growth factor beta in Human Renal Cells. Kidney Blood Press. Res. 45 , 850-862 (2020). Hayez, A. et al. High TMEM45A expression is correlated to epidermal keratinization. Exp. Dermatol. 23 , 339-344 (2014). Sasaki, T. et al. A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis. J. Allergy Clin. Immunol. 132 , 1111–1120.e4 (2013). Emrick, J. J. et al. Tissue-specific contributions of Tmem79 to atopic dermatitis and mast cell-mediated histaminergic itch. Proc. Natl Acad. Sci. U. S. A. 115 , E12091–E12100-e100 (2018). Han, J. et al. TMEM232 promotes the inflammatory response in atopic dermatitis via the nuclear factor-κB and signal transducer and activator of transcription 3 signalling pathways. Br. J. Dermatol. 189 , 195-209 (2023). Yoshihara, Y. et al. IL-10-producing regulatory B cells are decreased in patients with atopic dermatitis. J. Invest. Dermatol. 139 , 475-478 (2019). Moradkhani, S., Jafarzadeh, A., Bazargan-Harandi, N., Baneshi, M. R. & Mohammadi, M. M. Association of reduced count of interleukin-13-producing cells in breast milk with atopic dermatitis in infancy. Indian J. Med. Res. 148 , 317-322 (2018). Schoetzau, A. et al. Effect of exclusive breast-feeding and early solid food avoidance on the incidence of atopic dermatitis in high-risk infants at 1 year of age. Pediatr. Allergy Immunol. 13 , 234-242 (2002). Kull, I. et al. Breast-feeding reduces the risk for childhood eczema. J. Allergy Clin. Immunol. 116 , 657-661 (2005). Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics 129 , e827-e841 (2012). Snijders, B. E. et al. Breast-feeding duration and infant atopic manifestations, by maternal allergic status, in the first 2 years of life (KOALA study). J. Pediatr. 151 , 347-351, 51.e1-51.e2 (2007). Chuang, C. H. et al. Infant feeding practices and physician diagnosed atopic dermatitis: A prospective cohort study in Taiwan. Pediatr. Allergy Immunol. 22 , 43-49 (2011). Lee, K. S. et al. Does breast-feeding relate to development of atopic dermatitis in young Korean children?: Based on the fourth and fifth Korea national health and nutrition examination survey 2007-2012. Allergy Asthma Immunol. Res. 9 , 307-313 (2017). Hong, S. et al. Effect of prolonged breast-feeding on risk of atopic dermatitis in early childhood. Allergy Asthma Proc. 35 , 66-70 (2014). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-3312404","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":234005741,"identity":"8a3aef75-db9f-48b8-9b34-8de2c183c0e9","order_by":0,"name":"Eun-A Choi","email":"","orcid":"","institution":"Korea National Institute of Health, Korea Disease Control and Prevention Agency","correspondingAuthor":false,"prefix":"","firstName":"Eun-A","middleName":"","lastName":"Choi","suffix":""},{"id":234005742,"identity":"9d5e3628-0490-407e-96fc-10915c9767e9","order_by":1,"name":"Hee-Soo Han","email":"","orcid":"","institution":"Korea National Institute of Health, Korea Disease Control and Prevention Agency","correspondingAuthor":false,"prefix":"","firstName":"Hee-Soo","middleName":"","lastName":"Han","suffix":""},{"id":234005743,"identity":"7e4d8cf5-2dc7-4428-86a2-ee44084d6fb3","order_by":2,"name":"Guemkyung Nah","email":"","orcid":"","institution":"Korea National Institute of Health, Korea Disease Control and Prevention Agency","correspondingAuthor":false,"prefix":"","firstName":"Guemkyung","middleName":"","lastName":"Nah","suffix":""},{"id":234005744,"identity":"9fdefa8f-2887-4a5e-b878-73c7d2814d9c","order_by":3,"name":"So-Yeon Lee","email":"","orcid":"","institution":"University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"So-Yeon","middleName":"","lastName":"Lee","suffix":""},{"id":234005745,"identity":"8b5cdb90-44ae-4b4f-83f9-9159b68caf61","order_by":4,"name":"Young-Youl Kim","email":"","orcid":"","institution":"Korea National Institute of Health, Korea Disease Control and Prevention Agency","correspondingAuthor":false,"prefix":"","firstName":"Young-Youl","middleName":"","lastName":"Kim","suffix":""},{"id":234005746,"identity":"883f5c8c-3e78-4d8f-ab1f-9330b3674461","order_by":5,"name":"Soo-Jong Hong","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3UlEQVRIiWNgGAWjYFCCMyDCBs6VYeAhTksanMtDhBawisMkaJFvPHvwccGv8/K67QeYP3yoOAzUcvYBXi0GB84lG8/su2247UwCm+SMM0AtvO0G+LUwnDGT5u25zbjtBgMbM28bUAs/GwGHNYC1nLMHamH+/JcYLQwHgFp4fhxIBGphkGYEaeFtw6/D4MAZY2PehuTkbWcS2yR7zqTzsPEcI+CwGWcMH/P8sbPddvzw4Q8/Kqzl+HnS8GthkDjAwMAIdgpjA1iAkE8YGPhBCv8QVDYKRsEoGAUjGQAArxpEtLkQuw8AAAAASUVORK5CYII=","orcid":"","institution":"University of Ulsan College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Soo-Jong","middleName":"","lastName":"Hong","suffix":""},{"id":234005747,"identity":"ce54a2fa-14f9-4174-a7e3-6b65d2fa83b5","order_by":6,"name":"Hye-Ja Lee","email":"","orcid":"","institution":"Korea National Institute of Health, Korea Disease Control and Prevention Agency","correspondingAuthor":false,"prefix":"","firstName":"Hye-Ja","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2023-08-31 06:44:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3312404/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3312404/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":43532419,"identity":"ccb2e9a4-f99c-4f10-830a-b3326c40f2e2","added_by":"auto","created_at":"2023-09-22 13:24:31","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":305537,"visible":true,"origin":"","legend":"\u003cp\u003eParticipant inclusion and exclusion criteria\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3312404/v1/307bd1c401ef876897ef7743.jpeg"},{"id":45187717,"identity":"00024d72-b0b3-45cf-ad25-bd7e2417ab07","added_by":"auto","created_at":"2023-10-25 04:37:21","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":450508,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3312404/v1/cb644047-8d93-4331-a18c-3a93cb488eed.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of TMEM232 variant on blood lymphocyte counts in relation to incidence of infant atopic dermatitis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAtopic Dermatitis (AD) is a multifactorial chronic disease characterized by skin inflammation caused by both genetic and environmental factors \u003csup\u003e[1 2]\u003c/sup\u003e. The prevalence of AD is the highest among children \u003csup\u003e[3]\u003c/sup\u003e. Global Burden of Disease data confirms that AD affects patients' quality of life and has a high global burden \u003csup\u003e[4]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAD is a common inflammatory skin disease characterized by an imbalance between type 1 (Th1) and 2 (Th2) helper T cells \u003csup\u003e[5]\u003c/sup\u003e. During the progression of AD, IL-4 and IL-13, as central cytokines, promote Th2 differentiation by activating JAK-STAT signaling pathway \u003csup\u003e[6]\u003c/sup\u003e. In addition to the Th2-dominant immune responses seen in AD, immune cells such as B cells, dendritic cells, mast cells, and eosinophils also involve in the pathogenesis of AD by infiltrating lesions or secreting inflammatory mediators. \u003csup\u003e[7]\u003c/sup\u003e. Patients with AD have increased eosinophil counts and decreased lymphocyte counts in peripheral blood \u003csup\u003e[8 9]\u003c/sup\u003e. Studies have also reported that eosinophil-to-lymphocyte and neutrophil-to-lymphocyte ratios act as indicators for the improvement of clinical signs \u003csup\u003e[10]\u003c/sup\u003e and AD severity \u003csup\u003e[11]\u003c/sup\u003e in patients with AD. In addition, reduced lymphocyte counts, and elevated eosinophil and basophil counts have also been observed in patients with AD \u003csup\u003e[9]\u003c/sup\u003e. These studies suggest a relationship between the populations of immune cells and AD.\u003c/p\u003e \u003cp\u003eGenome-wide association studies (GWAS) have identified 62 genes associated with AD, most of which encode skin barrier proteins involved in the innate and adaptive immune responses \u003csup\u003e[12]\u003c/sup\u003e. \u003cem\u003eTMEM232\u003c/em\u003e (transmembrane protein 232), located on chromosome 5q22.1, is strongly associated with AD \u003csup\u003e[13\u0026ndash;15]\u003c/sup\u003e. Recently, haplotype analysis revealed that the H15 haplotype in the 5q22.1 region was associated with functional mutations in the \u003cem\u003eTMEM232\u003c/em\u003e gene \u003csup\u003e[16]\u003c/sup\u003e. \u003cem\u003eTMEM232\u003c/em\u003e has also been implicated in the development of several allergic diseases, the underlying mechanisms of which are thought to involve blood components. Additionally, some Asian populations, including Chinese and Japanese populations, are especially susceptible to allergic diseases owing to variations in \u003cem\u003eTMEM232\u003c/em\u003e\u003csup\u003e[13 14]\u003c/sup\u003e. However, an association between cord blood and the susceptibility to allergic diseases has not yet been reported in the Korean population. Here, we investigated the association between TMEM232 variant and blood parameters related to AD using Korean birth data and examined the potential relevance of TMEM232 variants in early childhood AD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy participants\u003c/h2\u003e \u003cp\u003eThis study analyzed the Cohort for Childhood Origin of Asthma and Allergic Disease (COCOA), a prospective longitudinal study that aimed to investigate the effects of environmental and genetic factors on the development of allergic diseases. The COCOA study recruited 3,004 mothers from the general population before 26 weeks of gestation. \u003csup\u003e[17]\u003c/sup\u003e. Of these, 2,846 children were born, and regular follow-up visits for health and environmental questionnaires and physician examinations were conducted at 6 months, 1 year, and yearly thereafter. The participants who withdrew consent, had twins, missing blood counts, missing AD information, or missing genotype information were excluded. Ultimately, 1,054 infants were selected for this study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This study was approved by the institutional review boards (IRBs) of Asan Medical Center (IRB no. 2008\u0026ndash;0616 and 2015\u0026ndash;1031), Samsung Medical Center (IRB no. 2009\u0026ndash;02\u0026ndash;021), Severance Hospital (IRB no. 4\u0026ndash;2008\u0026thinsp;\u0026minus;\u0026thinsp;0588), CHA Medical Center (IRB no. 2010\u0026ndash;010), and Seoul National University Hospital (IRB no. H-1401-086-550), and the Korea Disease Control and Prevention Agency (IRB no. 2020-03-06-C-A) and followed the guidelines of the Declaration of Helsinki (1975). Written informed consent was obtained from the parents of all the infants.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eDefinition of atopic dermatitis\u003c/h2\u003e \u003cp\u003eAD in infants was evaluated through questionnaires at each scheduled visit, inquiring whether a physician had ever diagnosed AD and if so, whether interventions were prescribed for the condition. AD was defined according to criteria described by Hanifin and Rajka. The AD phenotype of the infants was considered at one year of age. A pediatric allergist assessed the SCORing Atopic Dermatitis (SCORAD) index \u003csup\u003e[18]\u003c/sup\u003e. Higher numbers indicate greater severity, and the scale ranges from 0 to 103.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of leukocytes and IgE\u003c/h2\u003e \u003cp\u003eWhite blood cell counts and IgE levels (total IgE and milk-specific IgE) were measured. The percentage of blood leukocytes was calculated by using an automatic blood cell counter (XE-100; Sysmex Co., Kobe, Japan). Total serum IgE and milk-specific IgE levels were measured using a fluorescent enzyme immunoassay (AutoCAP System; Pharmacia Diagnostics AB, Uppsala, Sweden). Leukocyte and IgE levels in blood from infants at one-year-old were measured.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eQuestionnaire data\u003c/h2\u003e \u003cp\u003eThe questionnaire, which was based on the International Study of Asthma and Allergies in Childhood (ISAAC) was translated into Korean. The parents of the infants filled in a modified version of the questionnaire. The questionnaire consisted of (1) demographic factors, such as sex, date of birth, height, and weight; (2) symptom history related to AD; and (3) environmental factors related to allergic diseases, such as feeding method and residential patterns \u003csup\u003e[19]\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eGenotyping\u003c/h2\u003e \u003cp\u003eDNA samples were genotyped using the Korea Biobank Array (KoreanChip) designed by the Korean National Institute of Health, Korea. The KoreanChip comprises 833,535 markers, including more than 247,000 rare frequencies or functional variants derived from the sequencing data of 2500 Koreans. Genotyping data were removed for low-quality SNPs with a low variant call rate (\u0026lt;\u0026thinsp;98%), excessive heterozygosity, and sex discrepancies \u003csup\u003e[20]\u003c/sup\u003e. For further studies, we selected candidate TMEM232 variants associated with AD.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll data are expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SDs) for continuous variables and as frequencies and proportions for categorical variables. To compare groups, t-tests and ANOVA were conducted for continuous variables, and the chi-square test was performed for categorical variables. Based on their TMEM232 genotype, we divided the participants into three groups. We performed logistic regression analysis to determine the relationship between TMEM232 rs17132261 genetic variants and AD, adjusted for maternal age, maternal drinking status, and breastfeeding. The association between blood lymphocyte levels and TMEM232 rs17132261 genetic variants based on breastfeeding status was determined using linear regression, adjusted for maternal age and drinking status. All p-values were two-tailed, and p-values below 0.05 were considered statistically significant. All statistical analyses were performed using R software (version 4.1.3).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eCharacteristics of the study participants\u003c/h2\u003e \u003cp\u003eParticipants\u0026rsquo; characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A total of 269 infants were diagnosed with AD by doctors. Maternal lymphocytes were lower in infants with AD and showed significant differences according to the AD status of their offspring. The mean concentrations of total IgE and specific IgE to milk were 95.66 and 0.60 in the AD group, respectively, while 54.83 and 0.37 in the non-AD group, respectively. The mean eosinophils were 2.96 in the non-AD and 3.40 in the AD group, that is, the values were significantly different. In addition, the SCORAD index differed significantly between the two groups. TMEM232, a variant associated to AD, was also significantly associated with a higher risk of AD in the C allele.\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\u003eCharacteristics of mothers and one-year-old infants with atopic dermatitis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"15\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eNon-AD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c12\" namest=\"c7\"\u003e \u003cp\u003eAD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c15\" namest=\"c13\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c13\" namest=\"c11\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\" morerows=\"26\" rowspan=\"27\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMother, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e676\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e8.99(\u0026plusmn;\u0026thinsp;2.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e9.03(\u0026plusmn;\u0026thinsp;2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.857\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMonocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e540\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e6.81(\u0026plusmn;\u0026thinsp;1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e191\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e6.72(\u0026plusmn;\u0026thinsp;2.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.579\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLymphocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e542\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e21.24(\u0026plusmn;\u0026thinsp;8.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e191\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e19.78(\u0026plusmn;\u0026thinsp;6.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.039\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNeutrophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e535\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e70.51(\u0026plusmn;\u0026thinsp;10.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e71.8(\u0026plusmn;\u0026thinsp;8.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.119\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEosinophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e539\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e1.15(\u0026plusmn;\u0026thinsp;1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e1.22(\u0026plusmn;\u0026thinsp;2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.618\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBasophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e538\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e0.22(\u0026plusmn;\u0026thinsp;0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e188\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e0.20(\u0026plusmn;\u0026thinsp;0.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.363\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e635\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e110.79(\u0026plusmn;\u0026thinsp;316.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e103.62(\u0026plusmn;\u0026thinsp;288.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDer f-IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e514\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e5.03(\u0026plusmn;\u0026thinsp;12.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e5.81(\u0026plusmn;\u0026thinsp;15.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.533\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e36w Der f\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e413\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e299.19(\u0026plusmn;\u0026thinsp;1082.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e133\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e194.96(\u0026plusmn;\u0026thinsp;296.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.273\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePassive smoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.470\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePet ownership\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e235\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e29.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.810\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eInfant, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e782\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e8.88(\u0026plusmn;\u0026thinsp;2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e268\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e9.49(\u0026plusmn;\u0026thinsp;2.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMonocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e8.02(\u0026plusmn;\u0026thinsp;2.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e7.91(\u0026plusmn;\u0026thinsp;3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLymphocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e62.76(\u0026plusmn;\u0026thinsp;10.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e61.87(\u0026plusmn;\u0026thinsp;11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.247\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNeutrophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e25.66(\u0026plusmn;\u0026thinsp;10.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e267\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e26.04(\u0026plusmn;\u0026thinsp;10.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.604\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eEosinophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e785\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e2.96(\u0026plusmn;\u0026thinsp;1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e3.40(\u0026plusmn;\u0026thinsp;3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eBasophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e784\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e0.51(\u0026plusmn;\u0026thinsp;0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e0.55(\u0026plusmn;\u0026thinsp;0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.197\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e730\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e54.83(\u0026plusmn;\u0026thinsp;136.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e95.66(\u0026plusmn;\u0026thinsp;227.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMilk IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e730\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e0.37(\u0026plusmn;\u0026thinsp;0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e239\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e0.60(\u0026plusmn;\u0026thinsp;2.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.023\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSCORAD index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e624\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e0.28(\u0026plusmn;\u0026thinsp;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e203\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e8.04(\u0026plusmn;\u0026thinsp;9.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTMEM232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e406\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e51.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e60.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e308\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e39.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e36.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003e9.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c11\" namest=\"c10\"\u003e \u003cp\u003e4.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c14\" namest=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"15\"\u003eValues are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"15\"\u003ep-values are determined by t-test or chi-squared test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eParameters for the study participants according to TMEM232 genotype\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e lists the descriptive statistics for the study participants included in the analysis. The mean of lymphocytes at 1 year of age were 61.76, 63.49, and 63.17 in the CC, TC, and TT genotype, respectively, and there were significant differences among the three groups. The SCORAD index was the lowest in the case of TT genotype. There was a significant difference in the SCORAD index among the three groups.\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInfants parameters by TMEM232\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCC (n\u0026thinsp;=\u0026thinsp;568)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eTC (n\u0026thinsp;=\u0026thinsp;407)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTT (n\u0026thinsp;=\u0026thinsp;79)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiochemistry\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.60 (\u0026plusmn;\u0026thinsp;174.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.52 (\u0026plusmn;\u0026thinsp;164.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e47.18 (\u0026plusmn;\u0026thinsp;68.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.616\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMilk-IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e526\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.35 (\u0026plusmn;\u0026thinsp;0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.52 (\u0026plusmn;\u0026thinsp;1.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.49 (\u0026plusmn;\u0026thinsp;1.91)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.183\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.12 (\u0026plusmn;\u0026thinsp;2.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.96 (\u0026plusmn;\u0026thinsp;2.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.85 (\u0026plusmn;\u0026thinsp;2.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.515\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.10 (\u0026plusmn;\u0026thinsp;2.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.91 (\u0026plusmn;\u0026thinsp;2.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.66 (\u0026plusmn;\u0026thinsp;3.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.362\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.76 (\u0026plusmn;\u0026thinsp;11.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63.49 (\u0026plusmn;\u0026thinsp;9.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e63.17 (\u0026plusmn;\u0026thinsp;10.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.38 (\u0026plusmn;\u0026thinsp;10.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e405\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.95 (\u0026plusmn;\u0026thinsp;9.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e25.43 (\u0026plusmn;\u0026thinsp;9.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEosinophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.08 (\u0026plusmn;\u0026thinsp;2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.05 (\u0026plusmn;\u0026thinsp;2.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.11 (\u0026plusmn;\u0026thinsp;1.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.970\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e568\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.53 (\u0026plusmn;\u0026thinsp;0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e406\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.52 (\u0026plusmn;\u0026thinsp;0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.50 (\u0026plusmn;\u0026thinsp;0.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.826\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSCORAD index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e453\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.13 (\u0026plusmn;\u0026thinsp;6.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e310\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.60 (\u0026plusmn;\u0026thinsp;6.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.59 (\u0026plusmn;\u0026thinsp;2.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFeeding method\u003c/p\u003e \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\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.808\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e131\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormula feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\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=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eAssociation biochemistry parameters and feeding method\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e summarizes the descriptive statistics according to feeding method, which is an environmental indicator. The percentages of breast-feeding mixed feeding, and formula feeding were 22.45%, 68.88%, and 8.67%, respectively. Total IgE and milk-specific IgE levels were lower in breast-fed infants than in formula-fed infants. In addition, the mean lymphocyte count was lower in the breast-fed infants.\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 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eInfants biochemical parameters with respect to feeding method\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eBreast feeding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMixed feeding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eFormula feeding\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69.57 (\u0026plusmn;\u0026thinsp;123.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e665\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e68.70 (\u0026plusmn;\u0026thinsp;185.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27.85(\u0026plusmn;\u0026thinsp;48.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMilk-IgE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e206\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.55 (\u0026plusmn;\u0026thinsp;1.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e665\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.41 (\u0026plusmn;\u0026thinsp;1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.20 (\u0026plusmn;\u0026thinsp;0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.11 (\u0026plusmn;\u0026thinsp;2.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e712\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.00 (\u0026plusmn;\u0026thinsp;2.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.22 (\u0026plusmn;\u0026thinsp;2.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.710\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.16 (\u0026plusmn;\u0026thinsp;3.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.97 (\u0026plusmn;\u0026thinsp;2.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.55 (\u0026plusmn;\u0026thinsp;2.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.258\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.84 (\u0026plusmn;\u0026thinsp;10.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.38 (\u0026plusmn;\u0026thinsp;11.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e64.29 (\u0026plusmn;\u0026thinsp;9.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.274\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.23 (\u0026plusmn;\u0026thinsp;10.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e713\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.91 (\u0026plusmn;\u0026thinsp;10.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24.84 (\u0026plusmn;\u0026thinsp;8.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.499\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEosinophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.22 (\u0026plusmn;\u0026thinsp;2.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.07 (\u0026plusmn;\u0026thinsp;2.12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.72 (\u0026plusmn;\u0026thinsp;1.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBasophils, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e233\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.52 (\u0026plusmn;\u0026thinsp;0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e714\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.53 (\u0026plusmn;\u0026thinsp;0.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.53 (\u0026plusmn;\u0026thinsp;0.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.981\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAssociation between\u003c/b\u003e \u003cb\u003eTMEM232\u003c/b\u003e \u003cb\u003egenotype and AD\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe analyzed the association between the genotype of TMEM232 variant rs173132261 and AD using logistic regression (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). We found that infants with TC and CC genotype had a higher adjusted odds ratio (aOR) for the incidence of AD than infants with TT genotype (aOR 2.67; 95% CI 1.18\u0026ndash;6.06; p-value\u0026thinsp;=\u0026thinsp;0.018, aOR 3.55; 95% CI 1.59\u0026ndash;7.96; p-value\u0026thinsp;=\u0026thinsp;0.002). The incidence of AD was higher in individuals with the C allele than in those with the T allele.\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 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between \u003cem\u003eTMEM232\u003c/em\u003e (rs17132261) and infant atopic dermatitis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGenotype\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eaOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRef\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.18\u0026ndash;6.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.59\u0026ndash;7.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAdjusted for maternal age, maternal drinking status, feeding method\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eAssociation between\u003c/b\u003e \u003cb\u003eTMEM232\u003c/b\u003e \u003cb\u003egenotype and lymphocytes according to feeding method\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe association between lymphocytes and rs17132261 was assessed by dividing the infants into three groups according to feeding method (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). We confirmed that breast-fed infants with the CC genotype had lower lymphocyte levels than those with the TT genotype, with mean lymphocyte levels of 61.98 for CC and 67.86 for TT. The mean lymphocyte levels were 64.22 and 56.82 for CC and TT, respectively, indicating that infants with the TT genotype had lower lymphocyte counts. In mixed-fed infants, there was no significant difference in lymphocytes according to the TMEM232 genotype.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAssociation between \u003cem\u003eTMEM232\u003c/em\u003e (rs17132261) and infant lymphocytes according to feeding method\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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 \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eCC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eTC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTT\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.98 (\u0026plusmn;\u0026thinsp;10.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.15(\u0026plusmn;\u0026thinsp;10.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67.86 (\u0026plusmn;\u0026thinsp;8.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMixed feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.61 (\u0026plusmn;\u0026thinsp;11.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e63.42(\u0026plusmn;\u0026thinsp;9.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e62.33 (\u0026plusmn;\u0026thinsp;11.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormula feeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.22 (\u0026plusmn;\u0026thinsp;10.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.087\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.38(\u0026plusmn;\u0026thinsp;6.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56.82 (\u0026plusmn;\u0026thinsp;6.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAdjusted for maternal age, maternal drinking status\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAD is a multifactorial disease influenced by both genetic and environmental factors. The detection of AD in early life and the identification of genetic factors that interact with innocuous environmental factors are important for a timely diagnosis. In the present study, we identified \u003cem\u003eTMEM232\u003c/em\u003e as a candidate gene for AD in Korean infants by analyzing single-nucleotide polymorphisms reported in previous genome-wide studies on AD. Furthermore, we studied the association of \u003cem\u003eTMEM232\u003c/em\u003e genotypes and AD-associated phenotypes with decreased lymphocyte levels. We observed an association between the \u003cem\u003eTMEM232\u003c/em\u003e variant rs17132261 (C\u0026thinsp;\u0026gt;\u0026thinsp;T) in the cord blood and lymphocyte levels in infants with AD. Decreased lymphocyte levels are associated with an increased risk of developing AD in infants with the \u003cem\u003eTMEM232\u003c/em\u003e minor homozygous genotype (CC). These results indicate that the C allele of rs17132261 is a risk factor for infant AD and may manifest its effects through a decreased lymphocyte count.\u003c/p\u003e\n\u003cp\u003ePrevious studies suggested that \u003cem\u003eTMEM232\u003c/em\u003e is a potential genetic risk factor for AD. A GWAS conducted at the UK Biobank Europeans confirmed the association of \u003cem\u003eTMEM232\u003c/em\u003e with allergic diseases \u003csup\u003e[21]\u003c/sup\u003e, immunoglobulin type E in grass \u003csup\u003e[22]\u003c/sup\u003e, and AD \u003csup\u003e[23 24]\u003c/sup\u003e. Moreover, Japanese and Chinese Han GWAS have reported \u003cem\u003eTMEM232\u003c/em\u003e as a novel gene associated with AD \u003csup\u003e[13 14]\u003c/sup\u003e. Additionally, locus 5q22.1, which includes the AD-associated gene, \u003cem\u003eTMEM232\u003c/em\u003e, has been re-verified \u003csup\u003e[23]\u003c/sup\u003e and thoroughly sequenced in the Chinese population \u003csup\u003e[16]\u003c/sup\u003e. Genetic variants of \u003cem\u003eTMEM232\u003c/em\u003e are associated with several allergic diseases, including AD \u003csup\u003e[22 25\u0026ndash;27]\u003c/sup\u003e. A study on European participants confirmed an association between \u003cem\u003eTMEM232\u003c/em\u003e and allergic rhinitis \u003csup\u003e[22]\u003c/sup\u003e. \u003cem\u003eTMEM232\u003c/em\u003e has been confirmed to be associated with childhood food allergies \u003csup\u003e[25]\u003c/sup\u003e and asthma \u003csup\u003e[27]\u003c/sup\u003e. However, a GWAS \u003csup\u003e[28]\u003c/sup\u003e and candidate-gene approach \u003csup\u003e[29]\u003c/sup\u003e in Korean children showed only a modest association between the four SNPs of \u003cem\u003eTMEM232\u003c/em\u003e, excluding rs13361382, and a potential association between SCORing AD values and \u003cem\u003eTMEM232.\u003c/em\u003e In this study, we confirmed the association between AD and \u003cem\u003eTMEM232\u003c/em\u003e variant rs17132261, which is mediated by decreased lymphocyte levels in Korean infants.\u003c/p\u003e\n\u003cp\u003eTransmembrane proteins (TMEM) are firmly attached to cellular membranes. TMEMs play crucial roles in cellular physiology, including transportation, signal transduction, and intercellular communication \u003csup\u003e[30\u0026ndash;32]\u003c/sup\u003e. Although the specific functions of TMEM family proteins are still poorly characterized, new findings have highlighted the importance of the TMEM family as prognostic markers for various diseases \u003csup\u003e[33\u0026ndash;35]\u003c/sup\u003e. Among TMEM family proteins, TMEM45A has been reported to be correlated with epidermal keratinization through the Golgi network in both \u003cem\u003ein vivo\u003c/em\u003e and \u003cem\u003ein vitro\u003c/em\u003e models \u003csup\u003e[36]\u003c/sup\u003e. TMEM79 is a predisposing gene for AD which is related to lamellar granule system, mast cell degranulation, and skin barrier function \u003csup\u003e[7 37 38]\u003c/sup\u003e. TMEM232 has also been identified as a susceptibility gene for AD according to several GWAS \u003csup\u003e[13 14 16 24]\u003c/sup\u003e, the molecular function of which has recently been investigated \u003csup\u003e[39]\u003c/sup\u003e. Han et al. reported that TMEM232 is overexpressed in skin tissues of AD patients and mice, and inflamed skin cells and promotes inflammatory responses via the nuclear factor-\u0026kappa;B and STAT3 pathways, resulting in the formation of AD-like lesions \u003csup\u003e[39]\u003c/sup\u003e. Wu et al. reported the expression of TMEM232 in the granular layer and weak expression in the basal layer of skin samples from Chinese patients with AD using immunohistochemical staining \u003csup\u003e[24]\u003c/sup\u003e. No significant, positive expression of TMEM232 was found in the cytoplasm of lymphocytes around blood vessels \u003csup\u003e[24]\u003c/sup\u003e. Studies have shown that IL-10-producing B cells are decreased in AD patients, and IL-13-producing cells, which are supposed to be a type of lymphocyte, are also reduced in the breast milk of AD infants, suggesting an association between AD and lymphopenia \u003csup\u003e[40 41]\u003c/sup\u003e. Collectively, these studies suggested that TMEM232, a gene that regulates AD-related inflammation and lymphocytes, could be a target for AD treatment.\u003c/p\u003e\n\u003cp\u003eTMEM232 and lymphocytes were confirmed to be related to AD as genetic factors, and a marginal correlation showed that breastfeeding increased the risk of AD as an environmental factor. Several studies have reported that the role of breastfeeding in AD is inconsistent and still controversial \u003csup\u003e[42\u0026ndash;50]\u003c/sup\u003e. Recent studies reported that breastfeeding increases the incidence of AD \u003csup\u003e[46\u0026ndash;48]\u003c/sup\u003e. A cohort study in Taiwan showed that breastfeeding may be a risk factor for AD \u003csup\u003e[46]\u003c/sup\u003e. Korean studies have reported that breastfeeding is not associated with or does not increase the risk of AD \u003csup\u003e[47 48]\u003c/sup\u003e. Other studies have shown that prolonged breastfeeding increases the risk of AD \u003csup\u003e[49 50]\u003c/sup\u003e. These results are consistent with our findings that breastfeeding is a potential risk factor for AD in infants. Our results suggest that TMEM232 interacts with breastfeeding to decrease lymphocyte levels, which affects the risk of AD. Some studies have shown that breastfeeding protects against AD \u003csup\u003e[42 43]\u003c/sup\u003e. These results conflict with our findings because we did not adjust for maternal lifestyle, socioeconomic status, or educational level.\u003c/p\u003e\n\u003cp\u003eThe present study is valuable because it is easy to translate the obtained results to the general population because we analyzed the disease phenotypes of infants in a natural birth cohort and not in a case-control study. In particular, this is the first study to confirm the association between the blood lymphocyte counts of infants, infant TMEM232 variants, and AD in the Korean population.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study reports that the \u003cem\u003eTMEM232\u003c/em\u003e gene of cord blood is associated with infant blood lymphocyte counts, which are important in mounting normal immune responses and allergic diseases. Moreover, TMEM232 variant rs17132261 may be implicated in the lymphocyte-mediated pathogenesis of AD and other allergic diseases. Determining the association between \u003cem\u003eTMEM232\u003c/em\u003e genotype and AD may provide insights into the biological mechanisms underlying AD in the Korean population.\u003c/p\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u0026nbsp;\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Korea National Institute of Health (2020-NG-007-00, 2020-NG-007-01, 2020-NG-007-02, 2023-NI-008-00, 2017-E67002-00, 2017-E67002-01, 2017-E67002-02, 2020-E6702-00, and 2020-E6702-01) and the Bio \u0026amp; Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science \u0026amp; ICT (2014R1A2A1A10050687).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors had full access to the data. H.-J.L. was responsible for the integrity of the data and the accuracy of data analysis. H.-J. L. conceived and designed the study. E.A.C. performed the statistical analyses, and H.-S. H. G. K. N., S.Y.L., and H.-J. L. interpreted the data. E.A.C., G. K. N., and H.-J.L. wrote the initial draft of the manuscript, and S. J. H., Y.Y.K., and H. J. L. reviewed and edited the manuscript. All authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOMPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that there are no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAppiah, M. M. \u003cem\u003eet al.\u003c/em\u003e Atopic dermatitisReview of comorbidities and therapeutics. \u003cem\u003eAnn. Allergy Asthma Immunol.\u003c/em\u003e \u003cstrong\u003e129\u003c/strong\u003e, 142-149 (2022).\u003c/li\u003e\n\u003cli\u003eEichenfield, L. F. \u003cem\u003eet al.\u003c/em\u003e Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. \u003cem\u003eJ. Am. Acad. Dermatol.\u003c/em\u003e \u003cstrong\u003e70\u003c/strong\u003e, 338-351 (2014).\u003c/li\u003e\n\u003cli\u003eSilverberg, J. I. \u003cem\u003eet al.\u003c/em\u003e Atopic dermatitis in the pediatric population: A cross-sectional, international epidemiologic study. \u003cem\u003eAnn. Allergy Asthma Immunol.\u003c/em\u003e 126, 417\u0026ndash;428.e2 (2021).\u003c/li\u003e\n\u003cli\u003eLaughter, M. R. \u003cem\u003eet al.\u003c/em\u003e The global burden of atopic dermatitis: Lessons from the Global Burden of Disease Study 1990-2017. \u003cem\u003eBr. J. Dermatol.\u003c/em\u003e \u003cstrong\u003e184\u003c/strong\u003e, 304-309 (2021).\u003c/li\u003e\n\u003cli\u003eBieber, T. Atopic dermatitis. \u003cem\u003eN. Engl. J. Med.\u003c/em\u003e \u003cstrong\u003e358\u003c/strong\u003e, 1483-1494 (2008).\u003c/li\u003e\n\u003cli\u003eHuang, I. H., Chung, W. H., Wu, P. C. \u0026amp; Chen, C. B. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review. \u003cem\u003eFront. Immunol.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 1068260 (2022).\u003c/li\u003e\n\u003cli\u003eSaunders, S. P. \u003cem\u003eet al.\u003c/em\u003e Dysregulated skin barrier function in Tmem79 mutant mice promotes IL-17A-dependent spontaneous skin and lung inflammation. \u003cem\u003eAllergy\u003c/em\u003e \u003cstrong\u003e75\u003c/strong\u003e, 3216-3227 (2020).\u003c/li\u003e\n\u003cli\u003ePark, Y. M. \u0026amp; Bochner, B. S. Eosinophil survival and apoptosis in health and disease. \u003cem\u003eAllergy Asthma Immunol. Res.\u003c/em\u003e \u003cstrong\u003e2\u003c/strong\u003e, 87-101 (2010).\u003c/li\u003e\n\u003cli\u003eZeng-Yun-Ou, Z., Zhong-Yu, J. \u0026amp; Wei, L. Bidirectional associations between eosinophils, basophils, and lymphocytes with atopic dermatitis: A multivariable Mendelian randomization study. \u003cem\u003eFront. Immunol.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 1001911 (2022).\u003c/li\u003e\n\u003cli\u003e Hagino, T., Saeki, H., Fujimoto, E. \u0026amp; Kanda, N. The eosinophil-to-lymphocyte ratio acts as an indicator for improvement of clinical signs and itch by upadacitinib treatment in atopic dermatitis. \u003cem\u003eJ. Clin. Med.\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e (2023).\u003c/li\u003e\n\u003cli\u003e Dogru, M. \u0026amp; Citli, R. The neutrophil-lymphocyte ratio in children with atopic dermatitis: A case-control study. \u003cem\u003eClin. Ter.\u003c/em\u003e \u003cstrong\u003e168\u003c/strong\u003e, e262-e265 (2017).\u003c/li\u003e\n\u003cli\u003e Kader, H. A. \u003cem\u003eet al.\u003c/em\u003e Current insights into immunology and novel therapeutics of atopic dermatitis. \u003cem\u003eCells\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e (2021).\u003c/li\u003e\n\u003cli\u003e Hirota, T. \u003cem\u003eet al.\u003c/em\u003e Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. \u003cem\u003eNat. Genet.\u003c/em\u003e \u003cstrong\u003e44\u003c/strong\u003e, 1222-1226 (2012).\u003c/li\u003e\n\u003cli\u003e Sun, L. D. \u003cem\u003eet al.\u003c/em\u003e Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population. \u003cem\u003eNat. Genet.\u003c/em\u003e \u003cstrong\u003e43\u003c/strong\u003e, 690-694 (2011).\u003c/li\u003e\n\u003cli\u003e Tamari, M. \u0026amp; Hirota, T. Genome-wide association studies of atopic dermatitis. \u003cem\u003eJ. Dermatol.\u003c/em\u003e \u003cstrong\u003e41\u003c/strong\u003e, 213-220 (2014).\u003c/li\u003e\n\u003cli\u003e Zheng, J. \u003cem\u003eet al.\u003c/em\u003e Confirming the TMEM232 gene associated with atopic dermatitis through targeted capture sequencing. \u003cem\u003eSci. Rep.\u003c/em\u003e \u003cstrong\u003e11\u003c/strong\u003e, 21830 (2021).\u003c/li\u003e\n\u003cli\u003e Yang, H. J. \u003cem\u003eet al.\u003c/em\u003e The Cohort for Childhood Origin of Asthma and allergic diseases (COCOA) study: Design, rationale and methods. \u003cem\u003eBMC Pulm. Med.\u003c/em\u003e \u003cstrong\u003e14\u003c/strong\u003e, 109 (2014).\u003c/li\u003e\n\u003cli\u003e Severity scoring of atopic dermatitis: The SCORAD index. Consensus report of the European Task Force on Atopic Dermatitis. \u003cem\u003eDermatol. (Basel Switzerland)\u003c/em\u003e \u003cstrong\u003e186\u003c/strong\u003e, 23-31 (1993).\u003c/li\u003e\n\u003cli\u003e Yang, S. I. \u003cem\u003eet al.\u003c/em\u003e Effect of antibiotic use and mold exposure in infancy on allergic rhinitis in susceptible adolescents. \u003cem\u003eAnn. Allergy Asthma Immunol.\u003c/em\u003e \u003cstrong\u003e113\u003c/strong\u003e, 160\u0026ndash;165.e1 (2014).\u003c/li\u003e\n\u003cli\u003e Moon, S. \u003cem\u003eet al.\u003c/em\u003e The Korea biobank array: Design and identification of coding variants associated with blood biochemical traits. \u003cem\u003eSci. Rep.\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 1382 (2019).\u003c/li\u003e\n\u003cli\u003e Zhu, Z. \u003cem\u003eet al.\u003c/em\u003e Author Correction: A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases. \u003cem\u003eNat. Genet.\u003c/em\u003e \u003cstrong\u003e50\u003c/strong\u003e, 1753 (2018).\u003c/li\u003e\n\u003cli\u003e Ramasamy, A. \u003cem\u003eet al.\u003c/em\u003e A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cstrong\u003e128\u003c/strong\u003e, 996-1005 (2011).\u003c/li\u003e\n\u003cli\u003e Portelli, M. A., Hodge, E. \u0026amp; Sayers, I. Genetic risk factors for the development of allergic disease identified by genome-wide association. \u003cem\u003eClin. Exp. Allergy\u003c/em\u003e \u003cstrong\u003e45\u003c/strong\u003e, 21-31 (2015).\u003c/li\u003e\n\u003cli\u003e Wu, Y. Y. \u003cem\u003eet al.\u003c/em\u003e Scanning indels in the 5q22.1 region and identification of the TMEM232 susceptibility gene that is associated with atopic dermatitis in the Chinese Han population. \u003cem\u003eGene\u003c/em\u003e \u003cstrong\u003e617\u003c/strong\u003e, 17-23 (2017).\u003c/li\u003e\n\u003cli\u003e Hirota, T. \u003cem\u003eet al.\u003c/em\u003e Association study of childhood food allergy with genome-wide association studies-discovered loci of atopic dermatitis and eosinophilic esophagitis. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cstrong\u003e140\u003c/strong\u003e, 1713-1716 (2017).\u003c/li\u003e\n\u003cli\u003e Choi, B. Y., Han, M., Kwak, J. W. \u0026amp; Kim, T. H. Genetics and epigenetics in allergic rhinitis. \u003cem\u003eGenes\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e (2021).\u003c/li\u003e\n\u003cli\u003e Schoettler, N., Rodr\u0026iacute;guez, E., Weidinger, S. \u0026amp; Ober, C. Advances in asthma and allergic disease genetics: Is bigger always better? \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cstrong\u003e144\u003c/strong\u003e, 1495-1506 (2019).\u003c/li\u003e\n\u003cli\u003e Kim, K. W. \u003cem\u003eet al.\u003c/em\u003e Genome-wide association study of recalcitrant atopic dermatitis in Korean children. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cstrong\u003e136\u003c/strong\u003e, 678\u0026ndash;684.e4 (2015).\u003c/li\u003e\n\u003cli\u003e Kim, J. H. \u003cem\u003eet al.\u003c/em\u003e Association of genetic polymorphisms with atopic dermatitis, clinical severity and total IgE: A replication and extended study. \u003cem\u003eAllergy Asthma Immunol. Res.\u003c/em\u003e \u003cstrong\u003e10\u003c/strong\u003e, 397-405 (2018).\u003c/li\u003e\n\u003cli\u003e Zhang, N., Pan, H., Liang, X., Xie, J. \u0026amp; Han, W. The roles of transmembrane family proteins in the regulation of store-operated Ca2+ entry. \u003cem\u003eCell. Mol. Life Sci.\u003c/em\u003e \u003cstrong\u003e79\u003c/strong\u003e, 118 (2022).\u003c/li\u003e\n\u003cli\u003e Chen, J. \u003cem\u003eet al.\u003c/em\u003e TMEM196 inhibits lung cancer metastasis by regulating the Wnt/\u0026beta;-catenin signaling pathway. \u003cem\u003eJ. Cancer Res. Clin. Oncol.\u003c/em\u003e \u003cstrong\u003e149\u003c/strong\u003e, 653-667 (2023).\u003c/li\u003e\n\u003cli\u003e Zhang, S. \u003cem\u003eet al.\u003c/em\u003e TMEM116 is required for lung cancer cell motility and metastasis through PDK1 signaling pathway. \u003cem\u003eCell Death Dis.\u003c/em\u003e \u003cstrong\u003e12\u003c/strong\u003e, 1086 (2021).\u003c/li\u003e\n\u003cli\u003e Zhang, L., Liu, S. Y., Yang, X., Wang, Y. Q. \u0026amp; Cheng, Y. X. TMEM206 is a potential prognostic marker of hepatocellular carcinoma. \u003cem\u003eOncol. Lett.\u003c/em\u003e \u003cstrong\u003e20\u003c/strong\u003e, 174 (2020).\u003c/li\u003e\n\u003cli\u003e Deng, H. \u003cem\u003eet al.\u003c/em\u003e High expression of TMEM200A is associated with a poor prognosis and immune infiltration in gastric cancer. \u003cem\u003ePathol. Oncol. Res.\u003c/em\u003e \u003cstrong\u003e29\u003c/strong\u003e, 1610893 (2023).\u003c/li\u003e\n\u003cli\u003e Orphal, M. \u003cem\u003eet al.\u003c/em\u003e TMEM63C, a Potential Novel Target for Albuminuria Development, Is Regulated by MicroRNA-564 and transforming growth factor beta in Human Renal Cells. \u003cem\u003eKidney Blood Press. Res.\u003c/em\u003e \u003cstrong\u003e45\u003c/strong\u003e, 850-862 (2020).\u003c/li\u003e\n\u003cli\u003e Hayez, A. \u003cem\u003eet al.\u003c/em\u003e High TMEM45A expression is correlated to epidermal keratinization. \u003cem\u003eExp. Dermatol.\u003c/em\u003e \u003cstrong\u003e23\u003c/strong\u003e, 339-344 (2014).\u003c/li\u003e\n\u003cli\u003e Sasaki, T. \u003cem\u003eet al.\u003c/em\u003e A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cstrong\u003e132\u003c/strong\u003e, 1111\u0026ndash;1120.e4 (2013).\u003c/li\u003e\n\u003cli\u003e Emrick, J. J. \u003cem\u003eet al.\u003c/em\u003e Tissue-specific contributions of Tmem79 to atopic dermatitis and mast cell-mediated histaminergic itch. \u003cem\u003eProc. Natl Acad. Sci. U. S. A.\u003c/em\u003e \u003cstrong\u003e115\u003c/strong\u003e, E12091\u0026ndash;E12100-e100 (2018).\u003c/li\u003e\n\u003cli\u003e Han, J. \u003cem\u003eet al.\u003c/em\u003e TMEM232 promotes the inflammatory response in atopic dermatitis via the nuclear factor-\u0026kappa;B and signal transducer and activator of transcription 3 signalling pathways. \u003cem\u003eBr. J. Dermatol.\u003c/em\u003e \u003cstrong\u003e189\u003c/strong\u003e, 195-209 (2023).\u003c/li\u003e\n\u003cli\u003e Yoshihara, Y. \u003cem\u003eet al.\u003c/em\u003e IL-10-producing regulatory B cells are decreased in patients with atopic dermatitis. \u003cem\u003eJ. Invest. Dermatol.\u003c/em\u003e \u003cstrong\u003e139\u003c/strong\u003e, 475-478 (2019).\u003c/li\u003e\n\u003cli\u003e Moradkhani, S., Jafarzadeh, A., Bazargan-Harandi, N., Baneshi, M. R. \u0026amp; Mohammadi, M. M. Association of reduced count of interleukin-13-producing cells in breast milk with atopic dermatitis in infancy. \u003cem\u003eIndian J. Med. Res.\u003c/em\u003e \u003cstrong\u003e148\u003c/strong\u003e, 317-322 (2018).\u003c/li\u003e\n\u003cli\u003e Schoetzau, A. \u003cem\u003eet al.\u003c/em\u003e Effect of exclusive breast-feeding and early solid food avoidance on the incidence of atopic dermatitis in high-risk infants at 1 year of age. \u003cem\u003ePediatr. Allergy Immunol.\u003c/em\u003e \u003cstrong\u003e13\u003c/strong\u003e, 234-242 (2002).\u003c/li\u003e\n\u003cli\u003e Kull, I. \u003cem\u003eet al.\u003c/em\u003e Breast-feeding reduces the risk for childhood eczema. \u003cem\u003eJ. Allergy Clin. Immunol.\u003c/em\u003e \u003cstrong\u003e116\u003c/strong\u003e, 657-661 (2005).\u003c/li\u003e\n\u003cli\u003e Section on Breastfeeding. Breastfeeding and the use of human milk. \u003cem\u003ePediatrics\u003c/em\u003e \u003cstrong\u003e129\u003c/strong\u003e, e827-e841 (2012).\u003c/li\u003e\n\u003cli\u003e Snijders, B. E. \u003cem\u003eet al.\u003c/em\u003e Breast-feeding duration and infant atopic manifestations, by maternal allergic status, in the first 2 years of life (KOALA study). \u003cem\u003eJ. Pediatr.\u003c/em\u003e \u003cstrong\u003e151\u003c/strong\u003e, 347-351, 51.e1-51.e2 (2007).\u003c/li\u003e\n\u003cli\u003e Chuang, C. H. \u003cem\u003eet al.\u003c/em\u003e Infant feeding practices and physician diagnosed atopic dermatitis: A prospective cohort study in Taiwan. \u003cem\u003ePediatr. Allergy Immunol.\u003c/em\u003e \u003cstrong\u003e22\u003c/strong\u003e, 43-49 (2011).\u003c/li\u003e\n\u003cli\u003e Lee, K. S. \u003cem\u003eet al.\u003c/em\u003e Does breast-feeding relate to development of atopic dermatitis in young Korean children?: Based on the fourth and fifth Korea national health and nutrition examination survey 2007-2012. \u003cem\u003eAllergy Asthma Immunol. Res.\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 307-313 (2017).\u003c/li\u003e\n\u003cli\u003e Hong, S. \u003cem\u003eet al.\u003c/em\u003e Effect of prolonged breast-feeding on risk of atopic dermatitis in early childhood. \u003cem\u003eAllergy Asthma Proc.\u003c/em\u003e \u003cstrong\u003e35\u003c/strong\u003e, 66-70 (2014).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-3312404/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3312404/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAtopic dermatitis (AD) is caused by interactions between genetic susceptibility and environmental factors. Transmembrane protein 232 (\u003cem\u003eTMEM232\u003c/em\u003e) is one of the genes strongly implicated in AD. In the present study, we aimed to investigate the association between AD with variants within \u003cem\u003eTMEM232\u003c/em\u003e based on environmental factors, including feeding method. We performed a candidate gene association study involving the Cohort for Childhood Origins of Asthma and Allergic Diseases (infants, n\u0026thinsp;=\u0026thinsp;1,054). A single variant of the \u003cem\u003eTMEM232\u003c/em\u003e gene, rs17132261, was found to be significantly associated with AD. Subjects carrying the wild-type allele (C) of rs17132261 had lower blood lymphocyte count than those carrying the variant rs17132261 (T). Multiple logistic regression analysis showed a statistically significant association between \u003cem\u003eTMEM232\u003c/em\u003e gene polymorphism and an increased risk of AD in one year old infants. Moreover, rs17132261 was associated with decreased blood lymphocyte counts in infants breastfed for six months. The group with the CC genotype showed lower lymphocyte counts than CT and TT carriers when breastfed. Our findings demonstrate that the \u003cem\u003eTMEM232\u003c/em\u003e risk allele, in combination with breastfeeding, lowers the number of lymphocytes, which could be a potential risk factor for AD.\u003c/p\u003e","manuscriptTitle":"Effects of TMEM232 variant on blood lymphocyte counts in relation to incidence of infant atopic dermatitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-09-22 13:24:26","doi":"10.21203/rs.3.rs-3312404/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"84894b82-54c3-456a-a2e2-2fdeb1be1e78","owner":[],"postedDate":"September 22nd, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":24788633,"name":"Biological sciences/Genetics"},{"id":24788634,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2023-10-25T04:29:16+00:00","versionOfRecord":[],"versionCreatedAt":"2023-09-22 13:24:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3312404","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3312404","identity":"rs-3312404","version":["v1"]},"buildId":"J0_U0BvcaRcwD8yVFaRlm","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}