ACE Insertion/Deletion Gene Polymorphisms with DM Type II and Metabolic Syndrome among Sample of Jordanians

ACE Insertion/Deletion Gene Polymorphisms with DM Type II and Metabolic Syndrome among Sample of Jordanians | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article ACE Insertion/Deletion Gene Polymorphisms with DM Type II and Metabolic Syndrome among Sample of Jordanians Waleed Azayzeh, Ala' Alfreahat, Khaled Omar Khader, Mohamad-Said Almasri, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3823797/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 Objective MetS has gained an incredible interest worldwide on account of its increasing predominance with a prevalence rate of 14–32%, its incidence is increased by age for both genders. The present study was aimed to explore the relationship of angiotensin converting enzyme ( ACE ) insertion/deletion gene polymorphisms and the potential risk of development of diabetes mellitus type II and metabolic syndrome among a sample of Jordanians. Materials and Methods this case-control study included 148 type II diabetics; 127 MetS patients; and 241 normal subjects as a control group. ACE insertion/deletion gene polymorphisms were analyzed using PCR. Lipid profile, fasting blood glucose, and ACE activity was determined chemically. Apolipoprotein-A1 and plasma insulin levels were estimated by ELISA; and glycosylated hemoglobin was estimated by the micro-chromatographic method. Semiquantitative test strips were used for detecting microalbuminuria in urine. Results Regarding the criteria of metabolic syndrome, ID polymorphism was associated significantly with hypertension showing a positive risk ratio, microalbuminuria with positive risk ratios was associated significantly with II polymorphism and I allele, while, a significant negative risk ratios were shown between hypertension, microalbuminuria and DD polymorphism. Conclusion There is evidence that ID, II ACE gene polymorphisms and I allele may play a major role in the pathogenesis of metabolic syndrome along with diabetes mellitus type II in Jordanian population. Angiotensin-converting enzyme polymorphisms metabolic syndrome diabetes mellitus type II hyperlipidemia central obesity Figures Figure 1 Introduction MetS is defined as a group of metabolic abnormalities, including elevated levels of blood glucose, dyslipidemia, abdominal obesity and high blood pressure. It is mainly associated with increased rates of cardiovascular disease and diabetes mellitus Type II (DM type II) [ 1 ]. MetS has garnered incredible interest among researchers worldwide due to its increasing predominance. With a prevalence rate of 14–32%, its incidence increases by age for both genders. At present, Western-style diets and sedentary lifestyles amplify its incidence, so that it may reach the proportions of epidemicity. Among adults in USA, its prevalence was 34.2%, and recent reports indicated its increase [ 2 ]; subsequently, the prevalence of cardiovascular disease and DM type II is also likely to rise. The variation in MetS prevalence relies upon population characteristics (such as age, sex ethnicity and geographic area) [ 3 ]. MetS is a polygenic disease; many environmental and genetic factors may lead to its pathogenesis [ 4 ]. Therefore, it is important to study genetic factors as screening tools for identifying the high-risk individuals of MetS. Genome-level correlation analyzes some genetic predisposition to MetS, but none returned an acceptable result [ 5 ]. Genetic factors could explain the increased cardiovascular risk because many different genes are involved in regulating distinctive metabolic pathways. The mechanisms controlled by gene alleles include inflammatory processes and neurohormonal activity [renin-angiotensin aldosterone system (RAAS)] [ 6 ]. Several genetic loci linked to MetS and its components have been recognized by genome-wide association studies (GWAS). Recently, many European and Asian studies described those identified loci [ 7 ]. MetS is associated with a five-fold increase in the incidence of DM type II [ 8 ]. Hence, it’s very urgent to identify those with MetS as early as possible, so that interventions may help to prevent the development of complications including diabetes [ 9 ]. While there is limited recent knowledge of MetS prevalence in Jordan, its incidence appears to be as high as 51%, with a significantly (P < 0.05) higher prevalence in women (55.3%) than in men (46.4%). However, the prevalence of MetS, according to the WHO criteria, was 26.9%, with almost no differences between men and women [ 10 ]. ACE is a key enzyme in the renin-angiotensin aldosterone system that catalyzes the conversion of the angiotensin I to the powerful vasoconstrictor angiotensin II [ 11 ]. The ACE gene is composed of 26 exons spanning 21 kb on the long arm of chromosome 17 (17q23.3). It has a common polymorphism characterized by the insertion/presence (I allele) or deletion/absence (D allele) of a 287-bp Alu repeat sequence in intron 16. ACE activity in individuals with DD and ID polymorphisms is 65% and 31% higher, respectively, than those with II homozygotes [ 12 ]. Also, ACE significantly contributes to the pathogenesis of DM type II, as the RAAS blockade was demonstrated to improve insulin resis tance through reducing the harmful influence of angiotensin II on vasoconstriction, inflammation, apoptosis and death of pancreatic β cell, thus protecting the mass of β cell for producing insulin. There was, however, no evidence of a delay in or protection against insulin resistance and diabetes development [ 13 ]. A meta analysis reported the ACE insertion/deletion (I/D) gene polymorphisms as a candidate gene for essential hypertension and MetS development in a Chinese population. Therefore, the progress of MetS, DM type II and hypertension is highly affected by ACE insertion/deletion gene polymorphisms [ 14 ]. Based on the above-mentioned data, we conducted the present case control study to investigate the potential association between ACE I/D gene polymorphisms and the genetic susceptibility for MetS in Jordanians Materials and Methods 516 subjects participated in the study. They were divided into three different groups. Group I’s (148 type II subjects with diabetes) selection was based on the American Diabetes Association (ADA) criteria of DM type II [ 15 ]. Group II participants (127 patients with MetS) were selected on the basis of the WHO criteria of MetS [ 16 ]. Group III consisted of 241 healthy subjects. Patients with hepatic or renal disease or who were on ACE inhibitors were excluded. The healthy subjects, after exclusion of all possible endocrinologic or genetic disorders through history taking, examination, and relevant investigations, were included ethnically. Groups I and II were selected from those attending the General Medicine Department in Al-Karak Governmental Hospital and Islamic Hospital, Amman, Jordan for routine check-ups. Informed consent was obtained from each participant to participate and publish their data. The study was performed in line with the principles of The Code of Ethics of the World Medical Association ( https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/%20/t%20_blank ) (Declaration of Helsinki). Approval was granted by the Ethics Committee of University of Mutah (No: 201413). Sampling A 12–14 hour fasting blood sample was withdrawn from each participant and subdivided into EDTA-whole blood tubes for ACE gene polymorphisms and HbA1c assay, EDTA-plasma tubes for determining insulin, fluoride-plasma tubes for glucose estimation and plain tubes-serum for triacylglycerols (TGs), high-density lipoprotein-cholesterol (HDL-C), total cholesterol (Total-C), apolipoprotein-A (APO-A) and low-density lipoprotein-cholesterol (LDL-C) estimations. Morning urine mid-stream samples were collected for microalbuminuria assessment. All samples of plasma, serum, and urine were stored at – 20oC till assay. Biochemical Analyses ACE activity assay was estimated by a colorimetric method based on the Hurst and Lovell-Smith, procedure [ 17 ], using a kit supplied by LTA (Italy). Lipid profile assay, TGs, total-C and HDL-C were determined by enzymatic methods [ 18 – 20 ] using kits from Abcam (England), while LDL-C was estimated according to Friedwald et al.’s equation [ 21 ]. Apolipoprotein A-1 was measured by ELISA assay according to the method described by von Zychlinski et al. [ 22 ]; the kit used was provided from MyBioSource (USA). Microalbuminuria was done using semiquantitative test strips according to the method of Barrak et al. [ 23 ]; the kit for this was supplied by Roche Diagnostic Ltd. Glycemic Indices Fasting blood sugar was determined by glucose oxidase enzymatic method using a kit supplied from Abcam, England [ 24 ]. HbA1c was done according to mehod by Shrikanth and Anupama [ 25 ]. Fasting plasma insulin was assayed by immunoassay (EIA) according to the method described by Lamy et al. [ 26 ] using a kit supplied by Diagnostic Automation, USA. Homeostatic model assessment (HOMA)/Insulin resistance index (IR) method was used to determine the insulin resistance using following formula: HOMA/IR index = fasting blood glucose (mmol/l) x fasting insulin / 22.5, if the index is > 1.46, it is an indicator for insulin resistance [ 27 ]. ACE gene polymorphisms analysis After the extraction of DNA using blood DNA kit E.Z.N.A supplied by Omega Biotek, PCR was used for determining ACE I/D gene polymorphisms [ 28 ] using two primers (sense: 5'-CTG GAG ACC ACT CCC ATC CTT TCT- 3' and antisense: 5'-GAT GTG GCC ATC ACA TTC GTC AGAT-3') purchased from the integrated DNA technologies (IDT), USA. Each sample of DNA was subjected to a 3-program file in Thermal Cycler, the initial denaturation was done for 5 minutes at 95 o C. In addition, 30 cycles were carried out, 1 minute of denaturation at 95 o C followed by annealing for 45 seconds at 60 o C and extension for 1 minute at 72 o C. Lastly, the final extension was done for 5 minutes at 72 o C. Amplicons were subjected for gel electrophoresis. then, stained and visualized. In final visual representation showed a band at 190 bp for the homozygous DD polymorphism, a band at 490 bp for the homozygous II polymorphism. Furthermore, two bands at 490 bp and 190 bp were shown in the heterozygous ID polymorphism. Statistical Analyses The data entry was performed using the IBM-SPSS version 25.0. Tests of normality were performed for all quantitative data. The normally distributed data were presented in the form mean and standard deviation. t -test was used to detect the difference between means in the three groups. The test of association among qualitative groups of variables was used to detect the association between the genotype and allele groups with obesity, hypertension, and microalbuminuria. Risk ratio (Odds ratio, OR) was calculated for statistically significant associations among the qualitative groups. All tests of significance utilized were adjusted at the 5% level of significance. Results Table 1 shows that The group (DM Type II) had the highest mean±SD as regards HbA1c (11.1±1.4), whereas the group (MetS) showed the highest mean±SD as regards FBG, Insulin, ACE activity, LDLC, TGs, Total C, and HOMA index (198.7±16.0, 13.2±1.1, 41.2±6.8, 159.7±9.7, 200.8±11.8, 238.9±12.5, and 6.64±0.6 respectively). The control group showed the highest mean±SD for HDLC 53.2±2.5 and APOA 160.3±8.3 results. Table 1: Mean and standard deviation of test results by groups under study DM Type II (n=148) MetS (n=127) Control (n=241) Mean SD Mean SD Mean SD FBG 196.4 16.8 198.7 16.0 87.7 6.8 HbA1c 11.1 1.4 11.01 1.3 5.9 0.6 Insulin 12.9 1.2 13.2 1.1 3.5 0.4 ACE activity 31.7 3.7 41.2 6.8 14.9 1.4 LDLC 131.55 4.8 159.7 9.7 92.3 6.1 HDLC 40.86 3.1 39.4 3.8 53.2 2.5 TGs 165.5 6.7 200.8 11.8 94.8 5.4 Total C 204.6 10.3 238.9 12.5 173.6 4.6 APOA 151.6 6.3 136.1 9.4 160.3 8.3 HOMA index 6.3 0.7 6.64 0.6 0.973 0.1 Table 2 showed that a negative statistically significant difference was detected between the DM Type II and MetS group as regards ACE activity, LDLC, and TGs results (t-test= -14.4, -31.1, and -30.6, respectively) whereas a significant positive difference was detected for APOA results (t-test=16.1). A statistically significant difference was detected between the all results for groups DM Type II and the control group for FBG, HbA1c, Insulin, ACE activity, LDLC, HDLC, TGs, Total C, APOA, and HOMA index ( t -test=88.7, 48.2, 109.6, 62.1, 65.6, -42.8, 112.6, 40.3, -10.9, and 101.1 respectively). Similarly, a statistically significant difference was detected between the all results for groups MetS and the control group except for LDLC and APOA results, FBG, HbA1c, Insulin, ACE activity, HDLC, TGs, Total C, APOA, and HOMA index (t-test= 92.5, 48.8, 118.2, 57.2, -41.4, 116.8, 72.2, and 122.8 respectively). Table 2: Test of difference ( t -test) between the three groups under study DM Type II (n=148) Versus MetS (n=127) DM Type II (n=148) versus Control (n=241) MetS (n=127) versus Control (n=241) FBG -1.1 88.7* 92.5* HbA1c 0 .3 48.2* 48.8* Insulin -1.8 109.6* 118.2* ACE activity -14.4* 62.1* 57.2* LDLC -31.1* 65.6* 80.9 HDLC 3.3 -42.8* -41.4* TGs -30.6* 112.6* 116.8* Total C -24.7 40.3* 72.2* APOA 16.1* -10.9* -25.2 HOMA index -3.5 101.1* 122.8* The results illustrated that the distribution of ACE II, ID and DD gene polymorphisms was 43.9%, 37.8% and 18.3%, respectively, for type II subjects with diabetes, 34.6%, 42.5% and 22.9% for patients with MetS, respectively, while, it was 39.8%, 40.2% and 20%, respectively, for the controls. The distribution frequency for allele I was 62.8%, 55.9% and 60%, allele D was 37.2%, 44.1% and 40% for the three groups, respectively. Our results showed no significant differences between ACE gene polymorphisms and alleles distribution frequencies (Table 3). Table 3: ACE gene polymorphisms and alleles distribution frequencies in the studied groups Groups Polymorphism Allele II % ID % DD % I % D % Group I (DM type II) 65 (43.9%) 56 (37.8%) 27 (18.3%) 186 (62.8%) 110 (37.2%) Group II (MetS) 44 (34.6%) 54 (42.5%) 29 (22.9%) 142 (55.9%) 112 (44.1%) Group III (controls) 96 (39.8%) 97 (40.2%) 48 (20%) 289 (60%) 193 (40%) Table 4 shows the association and risk ratio between polymorphisms and alleles with obesity, hypertension, and microalbuminuria. A statistically significant association and positive risk ratio was detected between ID polymorphism and hypertension (λ 2 =4.3, OR=1.4, 95% CI= 1.01 – 1.88) while a significantly negative risk ratio was detected between DD polymorphism and hypertension (λ 2 =4.9, OR=0.7, 95% CI= 0.51 – 0.95). as regards microalbuminuria, a significantly positive risk ratio was detected between II polymorphism and I allele and microalbuminuria (λ 2 =3.2, OR= 1.4, 95% CI=1.02 – 1.92, and λ 2 =3.6, OR= 1.4, 95% CI=1.29 – 1,97 respectively). A significantly negative risk ratio was detected between DD polymorphism and microalbuminuria (λ 2 = 3.5, OR=0.7, 95% CI=0.51 – 0.95). Table 4: Association and risk ratio between polymorphisms and alleles with obesity, hypertension, and microalbuminuria Obesity Hypertension Microalbuminuria λ 2 OR 95% CI λ 2 OR 95% CI λ 2 OR 95% CI Polymorphisms II polymorphism - - - - - - 3.2* 1.4 1.02 – 1.92 ID polymorphism - - - 4.3* 1.4 1.01 – 1.88 - - - DD polymorphism - - - 4.9* 0.7 0.51 - 0.95 3.5* 0.7 0.51 – 0.95 Allele I allele - - - - - - 3.6* 1.4 1.29 – 1,97 D allele - - - - - - - - - Discussion Evidences from several studies have estimated the role of RAAS in the pathogenesis of MetS, DM type II, and related cardiovascular illness. The foremost mechanism by which RAAS may affect the risk of DM type II is by changing the level of aldosterone which has been found to be associated with insulin resistance and hyperinsulinemia which are major predisposing factors for MetS and DM type II. There is a lot of potential in the interaction between ACE gene polymorphisms to affect the DM type II and MetS risk [ 29 ]. Due to the inconsistent outcomes of these studies, ACE I/D gene polymorphisms were investigated in Jordanian patients with DM type II and MetS in the present study. In our study, the test of difference between patients with MetS, DM type II and the controls illustrated a statistically significant negative difference in the levels of ACE activity, LDLC and TGs between the groups of patients with MetS and DM Type II, while, there was a significant positive difference for the levels of APOA. Furthermore, a statistically significant difference was detected for the levels of total cholesterol, LDLC, HDLC, TGs, insulin level, FBG, HbA1c, ACE activity, APOA and HOMA index between patients with DM Type II group and the controls. Similarly, a statistically significant difference was shown between patients with MetS group of and the controls regarding the levels of all estimated parameters except for LDLC and APOA. The study of Oh et al. [ 30 ] stated a significant difference for the levels of FBG, TGs and HDLc in patients with MetS when compared to the controls, also, Al-Saikhan et al. [ 31 ] detected a significant difference regarding the levels of FBG and HDLC in patients with DM type II versus the controls, those findings are consistant with ours. The results of the present study illustrated that the distribution frequency of ACE II, ID and DD gene polymorphisms among the studied groups, in patients with DM type II group, it was the highest for II polymorphism and the lowest for DD polymorphism, while, in patients with MetS, it was the highest and the lowermost for DD and II polymorphisms, respectively. The distribution frequency of allele I was the highest for DM type II and the lowest for patients with MetS groups, on the other hand, for allele D, it was the highest and the lowest for MetS and DM type II groups of patients, respectively. Allele I was the dominant allele in patients with DM type II, while allele D was the dominant allele in patients with MetS. None of our results regarding ACE gene polymorphisms and alleles distribution frequencies showed statistically significant difference. In a previous study, the patients with diabetes group showed the least frequency for II polymorphism compared to ID and DD polymorphisms, the D allele was the dominant one [ 31 ]. In a mini review published in 2022, it was shown that the DD polymorphism is the most prevalent among the studied group of DM type II, but, they did not find any association between ACE I/D gene polymorphisms and DM type II [ 32 ]. In the study of Al-Harbi et al. [ 33 ], it was detected that ACE II, ID, and DD polymorphisms were different among Bahraini subjects with a a significantly high frequency for D allele in the studied group which showed an agreement with what obtained from previous studies among Caucasians, Africans and Arabs but inconsistent with the obtained results in the present study and in Chinese and Japanese studies. In a conducted study among Omanis population for the distribution frequency of ACE I/D gene polymorphisms and alleles, it was found that D allele frequency among Omanis is similar to the findings among Africans and other Arabs, but dissimilar to the obtained results among the Chinese and the Japanese [ 34 ]. Previously, it was reported that the distribution of ACE D allele varies from region to region, among Egyptians, Jordanians and Syrians, it was 67%, 66% and 60%, respectively [ 35 ]. Another studies stated that the distribution frequency of ACE I/D gene polymorphisms in patients with DM type II diabetes was higher for ID polymorphism than II and DD polymorphisms [ 36 , 37 ] with no significant difference between the polymorphic and allelic frequencies [ 36 , 38 ]. It was included that there was no strong association between ACE I/D gene polymorphisms and DM type II but regarding the predisposition factor for diabetes development, the DD polymorphism was significant [ 39 ]. In an Indian study conducted to clarify the association between ACE I/D polymorphisms, it was shown that DD polymorphism to be more frequent than II and ID polymorphisms in patients with MetS among North Indian population [ 40 ]. Two cross-sectional studies performed in Hungarian and Mexican populations reported significantly higher frequency of DD polymorphism and D allele among patients with MetS versus the non-metabolic ones [ 41 , 42 ]. Also, the association between ACE I/D polymorphisms and MetS was concluded in Chinese patients with DM type II [ 43 ]. Abouelfath et al. [ 44 , 45 ] highlighted the etiological role of ACE I/D polymorphisms in MetS and its components progress, additionally, DD polymorphism and D allele were shown to be protective against MetS development among adult Moroccan population and in Chilean subjects. In an Indonesian study, the frequent polymorphism among patients with DM type II was the DD variant and no association was found between ACE I/D polymorphisms and MetS & its related parameters [ 46 , 47 ]. This discrepancy in the results regarding the distribution frequency of ACE I/D gene polymorphisms, alleles and their participation in the development in DM type II, MetS and its related components could be attributed the ethnic variations among different population. By evaluating the association and risk ratio between polymorphisms and alleles with hypertension, microalbuminuria and obesity, the results revealed a statistically significant association indicating a positive risk and a negative risk ratios between hypertension and ID & DD polymorphisms, respectively. Another significantly positive risk and negative risk ratios were detected between microalbuminuria and II polymorphism & I allele and DD polymorphism, respectively. No association was noticed between obesity and any of the studied polymorphisms and alleles. It was found that no association between ACE I/D gene polymorphisms and hypertension [ 48 ] and obesity in Malay subjects, with weak interaction influence between D allele and lipid profiles [ 49 ]. There are other results proposing the association between ACE I/D polymorphisms and MetS without the involvement in hypertension pathogenesis, I allele was more frequent [ 50 ]. Simsek et al. [ 51 ] reported a high frequency of DD polymorphism and D allele of ACE gene among patients with MetS, but their results did not show significant difference when compared to the controls. in conclusion, there was no significant association between the polymorphic groups and waist circumference and blood pressure, those findings are inconsistent with what obtained by Nikzamir et al. [ 52 ] who identified the association between ACE I/D polymorphisms, D allele and DM type II but not with MetS. In a conducted case control study to investigate for the association between the molecular variants of ACE gene and microalbuminuria in patients with DM type II, it was shown that the carriers of DD polymorphism had greater urinary albumin excretion than the non-DD polymorphism carriers [ 53 ]. Also, it was reported that there was no significant association between ACE I/D gene polymorphisms and obesity as well as its related disorders, and I allele was statistically protective against hypertension compared to D allele [ 54 ]. On the other hand, no association was detected between ACE I/D gene polymorphisms and the patients of hypertension and DM type II in Emirati population, additionally, DD polymorphism was found to of protection role against hypertension in the subjects with obesity [ 55 ], which is not consistent with the results of Zhou et al. [ 56 ] who stated that DD polymorphism is a risk factor for hypertension but not for DM type II. There are several discrepancies between the present study and the previous studies including the ethnic variations or the bias of sampling, the background of the population selected in the study and racial differences including varied social or cultural issues. Abbreviations MetS Metabolic Syndrome ADA American Diabetes Association ACE Angiotensin converting enzyme APO-A Apolipoprotein-A ELISA Enzyme linked immunosorbent assay HDL-C High-density lipoprotein-cholesterol DM Diabetes mellitus LDL-C low-density lipoprotein-cholesterol RAAS Renin-angiotensin aldosterone system EIA Immunoassay I/D Insertion/deletion HOMA Homeostatic model assessment IR Insulin resistance index FBG Fasting blood glucose Declarations Conflict of interests: No potential conflict of interests relevant to this article was reported. (The manuscript had been read and approved by all the authors and each author believes that the manuscript represent honest work) Author contributions: SSM conceived designed and performed the experiments, WA, AA, KOK, MSA, LMM, MA, SJ, ROA, SA, DWS, and AD collected data, SSM and ZAA analyzed and interpreted results, SSM and WA wrote, prepared manuscript draft and did visualization, HMA and RM did critical revision of manuscript, SSM did editing of the manuscript, SSM, HMA and RD did the final approval of the manuscript version to be published. All authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript. Source of Funding : This research did not receive any specific grant from funding agencies in the public, commercial, or notfor- profit sectors Ethical approval : Approval was granted by the Ethics Committee of University of Mutah (No: 201413). 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BIOMEDICAL Rep 7:56–60. 10.3892/br.2017.920 Jones H (2022) Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism in Gaza Strip-Palestine and Type 2 Diabetic Nephropathy. Med Rep Case Stud 7(1):001–002. 10.2215/CJN.04140907 Al-Harbi ME, Farid ME, Gumaa AK, Singh J (2012) Genotypes and allele frequencies of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism among Bahraini population with type 2 diabetes mellitus and related diseases. Mol Cell Biochem 362(1–2):219–223. 10.1007/s11010-011-1146-1 Al-Hinai TA, Hassan OM, Simsek M, Al-Barwani H, Bayoumi R (2002) Genotypes and allele frequencies of angiotensin converting enzyme (ACE) insertion/deletion polymorphism among Omanis. J Sci Res Med Sci 4(1–2):25–27 PMID: 24019722. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174717/ Salem AH, Batzer MA (2009) High frequency of the D allele of the angiotensin-converting enzyme gene in Arabic populations. BMC Res Notes 2(1):1–5. 10.1186/1756-0500-2-99 Domingos BCA, Bonini-Domingos RC, Iacida CE, de Mattos BDC, de Mattos CL (2014) Angiotensin converting enzyme polymorphism in type 2 diabetes mellitus. Biomarkers and Genomic Medicine 6. https://doi.org/10.1016/j.bgm.2014.06.001 Yang M, Qiu C, Qun XU, Xiang H (2006) Association of Angiotensin Converting Enzyme Gene I/D Polymorphism With Type 2 Diabetes Mellitus. Biomed Environ Sci 19:323–327 PMID: 17044652. https://pubmed.ncbi.nlm.nih.gov/17044652/ Habibullah M, Akter F, Qin X, Lohani M, Aldughaim SM, Al-Kaabi Y (2021) Association between Angiotensin-Converting Enzyme-Insertion/Deletion Polymorphism and Diabetes Mellitus-2 in Saudi Population. Asian Pac J Cancer Prev 22(1):119–123. 10.31557/APJCP.2021.22.1.119 Barghash A, Al-Gharabli SI, Jweihan M, Tanbouz M, AlBarahmieh E, Hamad E, Al-Rifai N, AlHawari H, Tahtamouni LH Angiotensin Converting Enzyme (ACE) Gene Polymorphism in Jordanian Type-1 and Type-2 Diabetic Patients. Jordan J BiologicalSciences 2020Apr 1;13(2). https://jjbs.hu.edu.jo/files/vol13/n2/Paper%20Number%2012.pdf Mittal G, Gupta V, Haque FS, Khan SA (2011) Effect of angiotensin converting enzyme gene I/D polymorphism in patients with metabolic syndrome in North Indian population. Chin Med J (Engl) 124(1):45–48 PMID: 21362306. https://pubmed.ncbi.nlm.nih.gov/21362306/ Fiatal S, Szigethy E, Széles G, Tóth R, Ádány R (2011) Insertion/deletion polymorphism of angiotensin-1 converting enzyme is associated with metabolic syndrome in Hungarian adults. J Renin-Angiotensin Aldosterone Syst 12(4):531–538. https://doi.org/10.1177/1470320310394231 Alvarez-Aguilar C, Enríquez-Ramírez LM, Figueroa-Nuñez B, Gómez-García A, Rodríguez-Ayala E, Morán-Moguel C, Farías-Rodríguez MV, Mino-León D, López-Meza EJ (2007) Association between angiotensin-1 converting enzyme gene polymorphism and the metabolic syndrome in a Mexican population. EXPERIMENTAL and MOLECULARMEDICINE 39(3):327–334. https://www.nature.com/articles/emm200736 Lee Y, Tsai CRJ (2002) ACE Gene Insertion/Deletion Polymorphism Associated With 1998 World Health Organization Definition of Metabolic Syndrome in Chinese Type 2 Diabetic Patients. Diabetes Care 25:1002–1008. https://doi.org/10.2337/diacare.25.6.1002 Abouelfath R, Habbal R, Laaraj A, Khay K, Harraka M, Nadifi S (2018) ACE insertion/deletion polymorphism is positively associated with resistant hypertension in Morocco. Gene 658:178–183. https://doi.org/10.1016/j.gene.2018.03.028 Herrera LC, Castillo W, Estrada P, Mancilla B, Reyes G, Saavedra N, Guzmán N, Pamela Serón, Lanas F, Salazar AL (2016) Association of polymorphisms within the Renin-Angiotensin System with metabolic syndrome in a cohort of Chilean subjects. Arch Endocrinol Metab 60(3):190–198. https://doi.org/10.1590/2359-3997000000134 Sinorita H, Madiyan M, Pramono BR, Purnama BL, Ikhsan RM, Asdie HA (2010) ACE Gene Insertion/Deletion Polymorphism Among Patients with Type 2 Diabetes, and Its Relationship with Metabolic Syndrome at Sardjito Hospital Yogyakarta, Indonesia. Acta Med Indones-Indones J Intern Med 42(1):12–16 PMID: 20305326. https://pubmed.ncbi.nlm.nih.gov/20305326/ Nadalin S, Pavli´c DS, Peitl V, Karlovi´c D, Zatkovi´c L, Risti´c S, Tomljanovi´c BA, Jakovac H (2022) Association between Insertion-Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Treatment Response to Antipsychotic Medications: A Study of Antipsychotic-Naïve First-Episode Psychosis Patients and Nonadherent Chronic Psychosis Patients. Int J Mol Sci 23 12180, 11 pages. https://doi.org/10.3390/ijms232012180 Suokhrie S, Chaudhary V, Mishra S, Murry B (2023) Devi1 KN. Association of angiotensin-converting enzyme I/D polymorphism and apolipoprotein B with cardiometabolic abnormalities among young adults: a pilot study from Delhi. 2324–32. https://doi.org/10.1186/s43042-023-00432-y Apidi E, Sani IA, Johari ZKM, Rawi MIR, Farouk R, Al-shajrawi1 MO, Baig AA, Simbak BN (2020) Association of Angiotensin Converting Enzyme (ACE) Gene insertion/deletion (I/D) Polymorphism with Obesity and Obesity Related Phenotypes in Malay Subjects. JJBS 13(3):267–273. https://jjbs.hu.edu.jo/files/vol13/n3/Paper%20Number%202.pdf- Thomas NG, Tomlinson BP, Chan CN, JF, Sanderson EJ, Cockram SC, Critchley AJHJ (2001) Renin-Angiotensin System Gene Polymorphisms, Blood Pressure, Dyslipidemia, and Diabetes in Hong Kong Chinese. Diabetes Care 24:356–361. 10.2337/diacare.24.2.356 Simsek S, Tekes S, A Tuzcu KAT, Kılıc F, Culcu NN, Isık B, Akbas H (2013) Angiotensin-converting enzyme gene insertion/deletion polymorphism with metabolic syndrome in Turkish patients. J Endocrinol Invest 36(10):860–863. 10.3275/8967 Nikzamir A, Nakhjavani M, Golmohamadi T, Dibai L (2008) Association of Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism with Metabolic Syndrome in Iranians with Type 2 Diabetes Mellitus. Arch Iran Med 11(1):3–9 PMID: 18154415. https://pubmed.ncbi.nlm.nih.gov/18154415/ Dudley RC, Keavney B, Stratton M, Turner CR, Ratcliffe JP (1995) U.K. Prospective Diabetes Study. XV: Relationship of renin-angiotensin system gene polymorphisms with microalbuminuria in NIDDM. Kidney Int 48(6):1907–1911. 10.1038/ki.1995.490 Motawi TK, Shaker OG, Shahin NN, Ahmed NM (2016) Angiotensin-converting enzyme insertion/deletion polymorphism association with obesity and some related disorders in Egyptian females: a case-control observational study. Nutr metabolism 13(1):1–1. 10.1186/s12986-016-0127-5 Alsafar H, Hassoun A, Almazrouei S, Kamal W, Almaini M, Odama U, Rais N Association of angiotensin converting enzyme insertion-deletion polymorphism with hypertension in emiratis with type 2 diabetes mellitus and its interaction with obesity status. Disease markers 2015 Article ID 536041, 7 pages. 10.1155/2015/536041 Zhou YF, Yan H, Hou XP, Miao JL, Zhang J, Yin QX, Li JJ, Zhang XY, Li YY, Luo HL (2013) Association study of angiotensin converting enzyme gene polymorphism with elderly diabetic hypertension and lipids levels. Lipids Health Dis 12(1):1–4. http://www.lipidworld.com/content/12/1/187 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. 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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-3823797","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":264479939,"identity":"dd2128ad-2f2a-491c-8178-0a5726155759","order_by":0,"name":"Waleed Azayzeh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYFAC5oYDPAwMjA1A1oOECpAAcwMBLYxwLWwGH86AtDAS1sIA1cIgObMNKoIPGBw/2HjgDYOd7Hb2sweMeefVRvO3A7X8qNiGW8uZxIaDcxiSjXf25CU85t12PHfGYcYGxp4zt3FqMTuQ2HCYh4E5ccOBHANj3m3HchuAWpgZ2/BoOf8QpKU+ccP5NwbSvHOO5c4nqOUG2JbDiRtu5BhIzmyoyd1ASIv9jYdAvxgcN95w442ZwYdjB3I3ArUcxOcXyf7kwx/eVFTLbjifY/wgoaYud975wwcf/KjArQUCDOCsw2DyAAH1KKCOFMWjYBSMglEwQgAAA+Rmqk7Dz+YAAAAASUVORK5CYII=","orcid":"","institution":"Mutah University","correspondingAuthor":true,"prefix":"","firstName":"Waleed","middleName":"","lastName":"Azayzeh","suffix":""},{"id":264479940,"identity":"aa182758-3eff-4ea8-9522-04ea153e691b","order_by":1,"name":"Ala' Alfreahat","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Ala'","middleName":"","lastName":"Alfreahat","suffix":""},{"id":264479941,"identity":"0ac1abd3-98f9-4429-a354-2fa0e1704564","order_by":2,"name":"Khaled Omar Khader","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Khaled","middleName":"Omar","lastName":"Khader","suffix":""},{"id":264479942,"identity":"2becff5d-5ed0-43aa-96df-3cf31c27d502","order_by":3,"name":"Mohamad-Said Almasri","email":"","orcid":"","institution":"Ministry of Health","correspondingAuthor":false,"prefix":"","firstName":"Mohamad-Said","middleName":"","lastName":"Almasri","suffix":""},{"id":264479943,"identity":"0a088eb4-d5ea-474f-a007-52903395d2cf","order_by":4,"name":"Leena M. Mahmoud","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Leena","middleName":"M.","lastName":"Mahmoud","suffix":""},{"id":264479944,"identity":"8d0bf30b-a95a-4338-8603-17f40f58069a","order_by":5,"name":"Miqdad Alsarayreh","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Miqdad","middleName":"","lastName":"Alsarayreh","suffix":""},{"id":264479945,"identity":"1b76c9b4-6876-4a94-8fc2-4bfe58e18fab","order_by":6,"name":"Seif Jankhout","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Seif","middleName":"","lastName":"Jankhout","suffix":""},{"id":264479946,"identity":"b0f6a183-4a60-458b-aff6-9b5f580cd8bd","order_by":7,"name":"Rashed O. 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Salah","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Dania","middleName":"W.","lastName":"Salah","suffix":""},{"id":264479949,"identity":"70ffd948-edb8-4348-9e2f-ead1f9d5dea2","order_by":10,"name":"Abdallah Daradkeh","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Abdallah","middleName":"","lastName":"Daradkeh","suffix":""},{"id":264479950,"identity":"90517512-1d32-444e-8bfd-5a6449f6d04d","order_by":11,"name":"Ashraf A. Zaghloul","email":"","orcid":"","institution":"Alexandria University","correspondingAuthor":false,"prefix":"","firstName":"Ashraf","middleName":"A.","lastName":"Zaghloul","suffix":""},{"id":264479951,"identity":"4c85c881-d3ab-43c4-b143-95ec48196318","order_by":12,"name":"Heba M. Abd El Kareem","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Heba","middleName":"M. Abd El","lastName":"Kareem","suffix":""},{"id":264479952,"identity":"bd8abcc1-f582-4b60-af94-c954fafd5c8b","order_by":13,"name":"Rami Dwairi","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Rami","middleName":"","lastName":"Dwairi","suffix":""},{"id":264479953,"identity":"9fbeb5df-d497-4c09-a4ab-1f3a0e190fb2","order_by":14,"name":"Samir S. Mahgoub","email":"","orcid":"","institution":"Mutah University","correspondingAuthor":false,"prefix":"","firstName":"Samir","middleName":"S.","lastName":"Mahgoub","suffix":""}],"badges":[],"createdAt":"2023-12-30 10:59:34","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3823797/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3823797/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49137581,"identity":"463f479f-5596-4811-bd94-ca69e2596279","added_by":"auto","created_at":"2024-01-03 17:31:39","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":489584,"visible":true,"origin":"","legend":"\u003cp\u003e2% agarose gel showing the amplicons of the \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms. Lanes 2, 5, 8 and 9; two fragments (190 and 490 bp) (heterozygous ID polymorphism), lanes 3, 7 and 11; one fragment (190 bp) (homozygous DD polymorphism), lanes 4, 6, 10 and 12; one fragment (490 bp) (homozygous II polymorphism), the 100 bp DNA ladder is indicated in lane 1.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3823797/v1/3b5e7eb531325cb32942a87e.png"},{"id":50971052,"identity":"a551f98a-99ea-44cf-8ffe-135ed805d4a6","added_by":"auto","created_at":"2024-02-11 18:22:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":809860,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3823797/v1/7bc9c0ba-9bc0-4b2f-848c-f5368dc357df.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"ACE Insertion/Deletion Gene Polymorphisms with DM Type II and Metabolic Syndrome among Sample of Jordanians","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMetS is defined as a group of metabolic abnormalities, including elevated levels of blood glucose, dyslipidemia, abdominal obesity and high blood pressure. It is mainly associated with increased rates of cardiovascular disease and diabetes mellitus Type II (DM type II) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. MetS has garnered incredible interest among researchers worldwide due to its increasing predominance. With a prevalence rate of 14\u0026ndash;32%, its incidence increases by age for both genders. At present, Western-style diets and sedentary lifestyles amplify its incidence, so that it may reach the proportions of epidemicity. Among adults in USA, its prevalence was 34.2%, and recent reports indicated its increase [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]; subsequently, the prevalence of cardiovascular disease and DM type II is also likely to rise. The variation in MetS prevalence relies upon population characteristics (such as age, sex ethnicity and geographic area) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMetS is a polygenic disease; many environmental and genetic factors may lead to its pathogenesis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Therefore, it is important to study genetic factors as screening tools for identifying the high-risk individuals of MetS. Genome-level correlation analyzes some genetic predisposition to MetS, but none returned an acceptable result [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Genetic factors could explain the increased cardiovascular risk because many different genes are involved in regulating distinctive metabolic pathways. The mechanisms controlled by gene alleles include inflammatory processes and neurohormonal activity [renin-angiotensin aldosterone system (RAAS)] [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Several genetic loci linked to MetS and its components have been recognized by genome-wide association studies (GWAS). Recently, many European and Asian studies described those identified loci [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMetS is associated with a five-fold increase in the incidence of DM type II [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Hence, it\u0026rsquo;s very urgent to identify those with MetS as early as possible, so that interventions may help to prevent the development of complications including diabetes [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. While there is limited recent knowledge of MetS prevalence in Jordan, its incidence appears to be as high as 51%, with a significantly (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) higher prevalence in women (55.3%) than in men (46.4%). However, the prevalence of MetS, according to the WHO criteria, was 26.9%, with almost no differences between men and women [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eACE is a key enzyme in the renin-angiotensin aldosterone system that catalyzes the conversion of the angiotensin I to the powerful vasoconstrictor angiotensin II [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The ACE gene is composed of 26 exons spanning 21 kb on the long arm of chromosome 17 (17q23.3). It has a common polymorphism characterized by the insertion/presence (I allele) or deletion/absence (D allele) of a 287-bp Alu repeat sequence in intron 16. ACE activity in individuals with DD and ID polymorphisms is 65% and 31% higher, respectively, than those with II homozygotes [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAlso, ACE significantly contributes to the pathogenesis of DM type II, as the RAAS blockade was demonstrated to improve insulin resis tance through reducing the harmful influence of angiotensin II on vasoconstriction, inflammation, apoptosis and death of pancreatic β cell, thus protecting the mass of β cell for producing insulin. There was, however, no evidence of a delay in or protection against insulin resistance and diabetes development [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. A meta analysis reported the ACE insertion/deletion (I/D) gene polymorphisms as a candidate gene for essential hypertension and MetS development in a Chinese population. Therefore, the progress of MetS, DM type II and hypertension is highly affected by ACE insertion/deletion gene polymorphisms [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBased on the above-mentioned data, we conducted the present case control study to investigate the potential association between ACE I/D gene polymorphisms and the genetic susceptibility for MetS in Jordanians\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e516 subjects participated in the study. They were divided into three different groups. Group I\u0026rsquo;s (148 type II subjects with diabetes) selection was based on the American Diabetes Association (ADA) criteria of DM type II [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Group II participants (127 patients with MetS) were selected on the basis of the WHO criteria of MetS [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Group III consisted of 241 healthy subjects. Patients with hepatic or renal disease or who were on ACE inhibitors were excluded. The healthy subjects, after exclusion of all possible endocrinologic or genetic disorders through history taking, examination, and relevant investigations, were included ethnically. Groups I and II were selected from those attending the General Medicine Department in Al-Karak Governmental Hospital and Islamic Hospital, Amman, Jordan for routine check-ups. Informed consent was obtained from each participant to participate and publish their data. The study was performed in line with the principles of The Code of Ethics of the World Medical Association (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/%20/t%20_blank\u003c/span\u003e\u003cspan address=\"https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/%20/t%20_blank\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) (Declaration of Helsinki). Approval was granted by the Ethics Committee of University of Mutah (No: 201413).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eSampling\u003c/h2\u003e \u003cp\u003eA 12\u0026ndash;14 hour fasting blood sample was withdrawn from each participant and subdivided into EDTA-whole blood tubes for ACE gene polymorphisms and HbA1c assay, EDTA-plasma tubes for determining insulin, fluoride-plasma tubes for glucose estimation and plain tubes-serum for triacylglycerols (TGs), high-density lipoprotein-cholesterol (HDL-C), total cholesterol (Total-C), apolipoprotein-A (APO-A) and low-density lipoprotein-cholesterol (LDL-C) estimations. Morning urine mid-stream samples were collected for microalbuminuria assessment. All samples of plasma, serum, and urine were stored at \u0026ndash; 20oC till assay.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eBiochemical Analyses\u003c/h2\u003e \u003cp\u003eACE activity assay was estimated by a colorimetric method based on the Hurst and Lovell-Smith, procedure [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], using a kit supplied by LTA (Italy). Lipid profile assay, TGs, total-C and HDL-C were determined by enzymatic methods [\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] using kits from Abcam (England), while LDL-C was estimated according to Friedwald et al.\u0026rsquo;s equation [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Apolipoprotein A-1 was measured by ELISA assay according to the method described by von Zychlinski et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]; the kit used was provided from MyBioSource (USA). Microalbuminuria was done using semiquantitative test strips according to the method of Barrak et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]; the kit for this was supplied by Roche Diagnostic Ltd.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eGlycemic Indices\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eFasting blood sugar was determined by glucose oxidase enzymatic method using a kit supplied from Abcam, England [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHbA1c was done according to mehod by Shrikanth and Anupama [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eFasting plasma insulin was assayed by immunoassay (EIA) according to the method described by Lamy et al. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] using a kit supplied by Diagnostic Automation, USA.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eHomeostatic model assessment (HOMA)/Insulin resistance index (IR) method was used to determine the insulin resistance using following formula:\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eHOMA/IR index\u0026thinsp;=\u0026thinsp;fasting blood glucose (mmol/l) x fasting insulin / 22.5, if the index is \u0026gt;\u0026thinsp;1.46, it is an indicator for insulin resistance [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e\u003cem\u003eACE gene polymorphisms analysis\u003c/em\u003e\u003c/h2\u003e \u003cp\u003eAfter the extraction of DNA using blood DNA kit E.Z.N.A supplied by Omega Biotek, PCR was used for determining \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] using two primers (sense: 5'-CTG GAG ACC ACT CCC ATC CTT TCT- 3' and antisense: 5'-GAT GTG GCC ATC ACA TTC GTC AGAT-3') purchased from the integrated DNA technologies (IDT), USA. Each sample of DNA was subjected to a 3-program file in Thermal Cycler, the initial denaturation was done for 5 minutes at 95 \u003csup\u003eo\u003c/sup\u003eC. In addition, 30 cycles were carried out, 1 minute of denaturation at 95\u003csup\u003eo\u003c/sup\u003eC followed by annealing for 45 seconds at 60 \u003csup\u003eo\u003c/sup\u003eC and extension for 1 minute at 72 \u003csup\u003eo\u003c/sup\u003eC. Lastly, the final extension was done for 5 minutes at 72\u003csup\u003eo\u003c/sup\u003eC. Amplicons were subjected for gel electrophoresis. then, stained and visualized. In final visual representation showed a band at 190 bp for the homozygous DD polymorphism, a band at 490 bp for the homozygous II polymorphism. Furthermore, two bands at 490 bp and 190 bp were shown in the heterozygous ID polymorphism.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analyses\u003c/h2\u003e \u003cp\u003eThe data entry was performed using the IBM-SPSS version 25.0. Tests of normality were performed for all quantitative data. The normally distributed data were presented in the form mean and standard deviation. \u003cem\u003et\u003c/em\u003e-test was used to detect the difference between means in the three groups. The test of association among qualitative groups of variables was used to detect the association between the genotype and allele groups with obesity, hypertension, and microalbuminuria. Risk ratio (Odds ratio, OR) was calculated for statistically significant associations among the qualitative groups. All tests of significance utilized were adjusted at the 5% level of significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable 1 shows that The group (DM Type II) had the highest mean\u0026plusmn;SD as regards HbA1c (11.1\u0026plusmn;1.4), whereas the group (MetS) showed the highest mean\u0026plusmn;SD as regards FBG, Insulin, \u003cem\u003eACE\u003c/em\u003e activity, LDLC, TGs, Total C, and HOMA index (198.7\u0026plusmn;16.0, \u0026nbsp; 13.2\u0026plusmn;1.1, 41.2\u0026plusmn;6.8, 159.7\u0026plusmn;9.7, 200.8\u0026plusmn;11.8, 238.9\u0026plusmn;12.5, and 6.64\u0026plusmn;0.6 respectively). The control group showed the highest mean\u0026plusmn;SD for HDLC 53.2\u0026plusmn;2.5 and APOA 160.3\u0026plusmn;8.3 results.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1: Mean and standard deviation of test results by groups under study\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"504\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.571428571428573%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDM Type II (n=148)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.38095238095238%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetS (n=127)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (n=241)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003eMean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eFBG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e196.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e16.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e198.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e16.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e87.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eHbA1c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e11.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eInsulin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003e\u003cem\u003eACE\u003c/em\u003e activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e31.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e3.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e41.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eLDLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e131.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e159.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e9.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e92.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e6.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eHDLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e40.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e39.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e53.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eTGs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e165.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e200.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e94.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e5.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eTotal C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e204.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e238.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e173.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eAPOA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e151.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e136.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e9.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e160.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e8.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.047619047619047%\"\u003e\n \u003cp\u003eHOMA index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.095238095238095%\" valign=\"top\"\u003e\n \u003cp\u003e6.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.285714285714286%\" valign=\"top\"\u003e\n \u003cp\u003e0.973\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.714285714285714%\" valign=\"top\"\u003e\n \u003cp\u003e0.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eTable 2 showed that a negative statistically significant difference was detected between the DM Type II and MetS group as regards \u003cem\u003eACE\u003c/em\u003e activity, LDLC, and TGs results (t-test= -14.4, -31.1, and -30.6, respectively) whereas a significant positive difference was detected for APOA results (t-test=16.1). A statistically significant difference was detected between the all results for groups DM Type II and the control group for FBG, HbA1c, Insulin, \u003cem\u003eACE\u003c/em\u003e activity, LDLC, HDLC, TGs, Total C, APOA, and HOMA index (\u003cem\u003et\u003c/em\u003e-test=88.7, 48.2, 109.6, 62.1, 65.6, -42.8, 112.6, 40.3, -10.9, and 101.1 respectively). Similarly, a statistically significant difference was detected between the all results for groups MetS and the control group except for LDLC and APOA results, FBG, HbA1c, Insulin, ACE activity, HDLC, TGs, Total C, APOA, and HOMA index (t-test= 92.5, 48.8, 118.2, 57.2, -41.4, 116.8, 72.2, and 122.8 respectively). \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Test of difference (\u003cem\u003et\u003c/em\u003e-test) between the three groups under study\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003eDM Type II (n=148) Versus MetS (n=127)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003eDM Type II (n=148) versus Control (n=241)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003eMetS (n=127) versus Control (n=241)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eFBG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e-1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e88.7*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e92.5*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eHbA1c\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cspan dir=\"RTL\"\u003e0\u003c/span\u003e.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e48.2*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e48.8*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eInsulin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e-1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e109.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e118.2*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003e\u003cem\u003eACE\u003c/em\u003e activity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e-14.4*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e62.1*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e57.2*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eLDLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e-31.1*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e65.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e80.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eHDLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e-42.8*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e-41.4*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eTGs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e-30.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e112.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e116.8*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eTotal C\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e-24.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e40.3*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e72.2*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eAPOA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e16.1*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e-10.9*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e-25.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"8.465608465608465%\"\u003e\n \u003cp\u003eHOMA index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.746031746031747%\" valign=\"top\"\u003e\n \u003cp\u003e-3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.569664902998237%\" valign=\"top\"\u003e\n \u003cp\u003e101.1*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.21869488536155%\" valign=\"top\"\u003e\n \u003cp\u003e122.8*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe results illustrated that the distribution of \u003cem\u003eACE\u003c/em\u003e II, ID and DD gene polymorphisms was 43.9%, 37.8% and 18.3%, respectively, for type II subjects with diabetes, 34.6%, 42.5% and 22.9% for patients with MetS, respectively, while, it was 39.8%, 40.2% and 20%, respectively, for the controls. The distribution frequency for allele I was 62.8%, 55.9% and 60%, allele D was 37.2%, 44.1% and 40% for the three groups, respectively. Our results showed no significant differences between \u003cem\u003eACE\u003c/em\u003e gene polymorphisms and alleles distribution frequencies (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: \u003cem\u003eACE\u003c/em\u003e gene polymorphisms and alleles distribution frequencies in the studied groups\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"110%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.21212121212121%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"48.484848484848484%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Polymorphism\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.303030303030305%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; Allele\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;II \u0026nbsp;%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.36842105263158%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; ID %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; DD \u0026nbsp;%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.05263157894737%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;I \u0026nbsp; \u0026nbsp;%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.105263157894736%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;D \u0026nbsp; %\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eGroup I (DM type II)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e65 (43.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e56 (37.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e27 (18.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" valign=\"top\"\u003e\n \u003cp\u003e186 (62.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e110 (37.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eGroup II (MetS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e44 (34.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e54 (42.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e29 (22.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" valign=\"top\"\u003e\n \u003cp\u003e142 (55.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e112 (44.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003eGroup III (controls)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e96 (39.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.52577319587629%\" valign=\"top\"\u003e\n \u003cp\u003e97 (40.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e48 (20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.49484536082474%\" valign=\"top\"\u003e\n \u003cp\u003e289 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.402061855670103%\" valign=\"top\"\u003e\n \u003cp\u003e193 (40%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 shows the association and risk ratio between polymorphisms and alleles with obesity, hypertension, and microalbuminuria. A statistically significant association and positive risk ratio was detected between ID polymorphism and hypertension (\u0026lambda;\u003csup\u003e2\u003c/sup\u003e=4.3, OR=1.4, 95% CI= 1.01 \u0026ndash; 1.88) while a significantly negative risk ratio was detected between DD polymorphism and hypertension (\u0026lambda;\u003csup\u003e2\u003c/sup\u003e=4.9, OR=0.7, 95% CI= 0.51 \u0026ndash; 0.95). as regards microalbuminuria, a significantly positive risk ratio was detected between II polymorphism and I allele and microalbuminuria (\u0026lambda;\u003csup\u003e2\u003c/sup\u003e=3.2, OR= 1.4, 95% CI=1.02 \u0026ndash; 1.92, and \u0026lambda;\u003csup\u003e2\u003c/sup\u003e=3.6, OR= 1.4, 95% CI=1.29 \u0026ndash; 1,97 respectively). A significantly negative risk ratio was detected between DD polymorphism and microalbuminuria (\u0026lambda;\u003csup\u003e2\u003c/sup\u003e= 3.5, OR=0.7, 95% CI=0.51 \u0026ndash; 0.95).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4: Association and risk ratio between polymorphisms and alleles with obesity, hypertension, and microalbuminuria\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"642\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.626168224299064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.560747663551403%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eObesity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.97196261682243%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"30.8411214953271%\" colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eMicroalbuminuria\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lambda;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lambda;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lambda;\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003ePolymorphisms\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003eII polymorphism\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e3.2*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e1.02 \u0026ndash; 1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003eID polymorphism\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e4.3*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e1.01 \u0026ndash; 1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003eDD polymorphism\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e4.9*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e0.51 - 0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e3.5*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e0.51 \u0026ndash; 0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003eAllele\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003eI allele\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e3.6*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e1.29 \u0026ndash; 1,97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"19.565217391304348%\" valign=\"top\"\u003e\n \u003cp\u003eD allele\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"4.3478260869565215%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.6770186335403725%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.627329192546584%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.832298136645963%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.751552795031056%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.453416149068323%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.093167701863354%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.198757763975156%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; -\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eEvidences from several studies have estimated the role of RAAS in the pathogenesis of MetS, DM type II, and related cardiovascular illness. The foremost mechanism by which RAAS may affect the risk of DM type II is by changing the level of aldosterone which has been found to be associated with insulin resistance and hyperinsulinemia which are major predisposing factors for MetS and DM type II. There is a lot of potential in the interaction between \u003cem\u003eACE\u003c/em\u003e gene polymorphisms to affect the DM type II and MetS risk [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Due to the inconsistent outcomes of these studies, \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms were investigated in Jordanian patients with DM type II and MetS in the present study.\u003c/p\u003e \u003cp\u003eIn our study, the test of difference between patients with MetS, DM type II and the controls illustrated a statistically significant negative difference in the levels of ACE activity, LDLC and TGs between the groups of patients with MetS and DM Type II, while, there was a significant positive difference for the levels of APOA. Furthermore, a statistically significant difference was detected for the levels of total cholesterol, LDLC, HDLC, TGs, insulin level, FBG, HbA1c, ACE activity, APOA and HOMA index between patients with DM Type II group and the controls. Similarly, a statistically significant difference was shown between patients with MetS group of and the controls regarding the levels of all estimated parameters except for LDLC and APOA. The study of Oh et al. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] stated a significant difference for the levels of FBG, TGs and HDLc in patients with MetS when compared to the controls, also, Al-Saikhan et al. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] detected a significant difference regarding the levels of FBG and HDLC in patients with DM type II versus the controls, those findings are consistant with ours.\u003c/p\u003e \u003cp\u003eThe results of the present study illustrated that the distribution frequency of \u003cem\u003eACE\u003c/em\u003e II, ID and DD gene polymorphisms among the studied groups, in patients with DM type II group, it was the highest for II polymorphism and the lowest for DD polymorphism, while, in patients with MetS, it was the highest and the lowermost for DD and II polymorphisms, respectively. The distribution frequency of allele I was the highest for DM type II and the lowest for patients with MetS groups, on the other hand, for allele D, it was the highest and the lowest for MetS and DM type II groups of patients, respectively. Allele I was the dominant allele in patients with DM type II, while allele D was the dominant allele in patients with MetS. None of our results regarding \u003cem\u003eACE\u003c/em\u003e gene polymorphisms and alleles distribution frequencies showed statistically significant difference.\u003c/p\u003e \u003cp\u003eIn a previous study, the patients with diabetes group showed the least frequency for II polymorphism compared to ID and DD polymorphisms, the D allele was the dominant one [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In a mini review published in 2022, it was shown that the DD polymorphism is the most prevalent among the studied group of DM type II, but, they did not find any association between \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms and DM type II [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. In the study of Al-Harbi et al. [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e], it was detected that \u003cem\u003eACE\u003c/em\u003e II, ID, and DD polymorphisms were different among Bahraini subjects with a a significantly high frequency for D allele in the studied group which showed an agreement with what obtained from previous studies among Caucasians, Africans and Arabs but inconsistent with the obtained results in the present study and in Chinese and Japanese studies. In a conducted study among Omanis population for the distribution frequency of \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms and alleles, it was found that D allele frequency among Omanis is similar to the findings among Africans and other Arabs, but dissimilar to the obtained results among the Chinese and the Japanese [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Previously, it was reported that the distribution of \u003cem\u003eACE\u003c/em\u003e D allele varies from region to region, among Egyptians, Jordanians and Syrians, it was 67%, 66% and 60%, respectively [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Another studies stated that the distribution frequency of \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms in patients with DM type II diabetes was higher for ID polymorphism than II and DD polymorphisms [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e] with no significant difference between the polymorphic and allelic frequencies [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. It was included that there was no strong association between \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms and DM type II but regarding the predisposition factor for diabetes development, the DD polymorphism was significant [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn an Indian study conducted to clarify the association between \u003cem\u003eACE\u003c/em\u003e I/D polymorphisms, it was shown that DD polymorphism to be more frequent than II and ID polymorphisms in patients with MetS among North Indian population [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Two cross-sectional studies performed in Hungarian and Mexican populations reported significantly higher frequency of DD polymorphism and D allele among patients with MetS versus the non-metabolic ones [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Also, the association between \u003cem\u003eACE\u003c/em\u003e I/D polymorphisms and MetS was concluded in Chinese patients with DM type II [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Abouelfath et al. [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e] highlighted the etiological role of \u003cem\u003eACE\u003c/em\u003e I/D polymorphisms in MetS and its components progress, additionally, DD polymorphism and D allele were shown to be protective against MetS development among adult Moroccan population and in Chilean subjects. In an Indonesian study, the frequent polymorphism among patients with DM type II was the DD variant and no association was found between \u003cem\u003eACE\u003c/em\u003e I/D polymorphisms and MetS \u0026amp; its related parameters [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. This discrepancy in the results regarding the distribution frequency of \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms, alleles and their participation in the development in DM type II, MetS and its related components could be attributed the ethnic variations among different population.\u003c/p\u003e \u003cp\u003eBy evaluating the association and risk ratio between polymorphisms and alleles with hypertension, microalbuminuria and obesity, the results revealed a statistically significant association indicating a positive risk and a negative risk ratios between hypertension and ID \u0026amp; DD polymorphisms, respectively. Another significantly positive risk and negative risk ratios were detected between microalbuminuria and II polymorphism \u0026amp; I allele and DD polymorphism, respectively. No association was noticed between obesity and any of the studied polymorphisms and alleles. It was found that no association between \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms and hypertension [\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e] and obesity in Malay subjects, with weak interaction influence between D allele and lipid profiles [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. There are other results proposing the association between \u003cem\u003eACE\u003c/em\u003e I/D polymorphisms and MetS without the involvement in hypertension pathogenesis, I allele was more frequent [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. Simsek et al. [\u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e] reported a high frequency of DD polymorphism and D allele of \u003cem\u003eACE\u003c/em\u003e gene among patients with MetS, but their results did not show significant difference when compared to the controls. in conclusion, there was no significant association between the polymorphic groups and waist circumference and blood pressure, those findings are inconsistent with what obtained by Nikzamir et al. [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e] who identified the association between ACE I/D polymorphisms, D allele and DM type II but not with MetS. In a conducted case control study to investigate for the association between the molecular variants of \u003cem\u003eACE\u003c/em\u003e gene and microalbuminuria in patients with DM type II, it was shown that the carriers of DD polymorphism had greater urinary albumin excretion than the non-DD polymorphism carriers [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Also, it was reported that there was no significant association between \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms and obesity as well as its related disorders, and I allele was statistically protective against hypertension compared to D allele [\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. On the other hand, no association was detected between \u003cem\u003eACE\u003c/em\u003e I/D gene polymorphisms and the patients of hypertension and DM type II in Emirati population, additionally, DD polymorphism was found to of protection role against hypertension in the subjects with obesity [\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e], which is not consistent with the results of Zhou et al. [\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e] who stated that DD polymorphism is a risk factor for hypertension but not for DM type II.\u003c/p\u003e \u003cp\u003eThere are several discrepancies between the present study and the previous studies including the ethnic variations or the bias of sampling, the background of the population selected in the study and racial differences including varied social or cultural issues.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.146422628951747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMetS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eMetabolic Syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.976705490848586%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eADA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.940099833610645%\" valign=\"top\"\u003e\n \u003cp\u003eAmerican Diabetes Association\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.146422628951747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eACE\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eAngiotensin converting enzyme\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.976705490848586%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAPO-A\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.940099833610645%\" valign=\"top\"\u003e\n \u003cp\u003eApolipoprotein-A\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.146422628951747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eELISA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eEnzyme linked immunosorbent assay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.976705490848586%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHDL-C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.940099833610645%\" valign=\"top\"\u003e\n \u003cp\u003eHigh-density lipoprotein-cholesterol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.146422628951747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDM\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.976705490848586%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLDL-C\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.940099833610645%\" valign=\"top\"\u003e\n \u003cp\u003elow-density lipoprotein-cholesterol\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.146422628951747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRAAS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eRenin-angiotensin aldosterone system\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.976705490848586%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eEIA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.940099833610645%\" valign=\"top\"\u003e\n \u003cp\u003eImmunoassay \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.146422628951747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eI/D\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eInsertion/deletion\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.976705490848586%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHOMA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.940099833610645%\" valign=\"top\"\u003e\n \u003cp\u003eHomeostatic model assessment\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.146422628951747%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"37.93677204658902%\" valign=\"top\"\u003e\n \u003cp\u003eInsulin resistance index\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.976705490848586%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFBG\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.940099833610645%\" valign=\"top\"\u003e\n \u003cp\u003eFasting blood glucose\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interests:\u0026nbsp;\u003c/strong\u003eNo potential conflict of interests relevant to this article was reported. (The manuscript had been read and approved by all the authors and each author believes that the manuscript represent honest work)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSSM conceived designed and performed the experiments, WA, AA, KOK, MSA, LMM, MA, SJ, ROA, SA, DWS, and AD collected data, SSM and ZAA analyzed and interpreted results, SSM and WA wrote, prepared manuscript draft and did visualization, HMA and RM did critical revision of manuscript, SSM did editing of the manuscript, SSM, HMA and RD did the final approval of the manuscript version to be published.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors have critically reviewed and approved the final draft and are responsible for the content and similarity index of the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource of Funding :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or notfor- profit sectors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval :\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eApproval was granted by the Ethics Committee of University of Mutah (No: 201413).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKelishadi R, Hovsepian S, Haghjooy Javanmard S (2018) A Systematic review of single nucleotide polymorphisms associated with metabolic syndrome in children and adolescents. 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Disease markers 2015 Article ID 536041, 7 pages. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2015/536041\u003c/span\u003e\u003cspan address=\"10.1155/2015/536041\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou YF, Yan H, Hou XP, Miao JL, Zhang J, Yin QX, Li JJ, Zhang XY, Li YY, Luo HL (2013) Association study of angiotensin converting enzyme gene polymorphism with elderly diabetic hypertension and lipids levels. Lipids Health Dis 12(1):1\u0026ndash;4. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.lipidworld.com/content/12/1/187\u003c/span\u003e\u003cspan address=\"http://www.lipidworld.com/content/12/1/187\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\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":"Angiotensin-converting enzyme, polymorphisms, metabolic syndrome, diabetes mellitus type II, hyperlipidemia, central obesity","lastPublishedDoi":"10.21203/rs.3.rs-3823797/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3823797/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eMetS has gained an incredible interest worldwide on account of its increasing predominance with a prevalence rate of 14\u0026ndash;32%, its incidence is increased by age for both genders. The present study was aimed to explore the relationship of angiotensin converting enzyme (\u003cem\u003eACE\u003c/em\u003e) insertion/deletion gene polymorphisms and the potential risk of development of diabetes mellitus type II and metabolic syndrome among a sample of Jordanians.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003ethis case-control study included 148 type II diabetics; 127 MetS patients; and 241 normal subjects as a control group. \u003cem\u003eACE\u003c/em\u003e insertion/deletion gene polymorphisms were analyzed using PCR. Lipid profile, fasting blood glucose, and \u003cem\u003eACE\u003c/em\u003e activity was determined chemically. Apolipoprotein-A1 and plasma insulin levels were estimated by ELISA; and glycosylated hemoglobin was estimated by the micro-chromatographic method. Semiquantitative test strips were used for detecting microalbuminuria in urine.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eRegarding the criteria of metabolic syndrome, ID polymorphism was associated significantly with hypertension showing a positive risk ratio, microalbuminuria with positive risk ratios was associated significantly with II polymorphism and I allele, while, a significant negative risk ratios were shown between hypertension, microalbuminuria and DD polymorphism.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThere is evidence that ID, II \u003cem\u003eACE\u003c/em\u003e gene polymorphisms and I allele may play a major role in the pathogenesis of metabolic syndrome along with diabetes mellitus type II in Jordanian population.\u003c/p\u003e","manuscriptTitle":"ACE Insertion/Deletion Gene Polymorphisms with DM Type II and Metabolic Syndrome among Sample of Jordanians","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-03 17:31:34","doi":"10.21203/rs.3.rs-3823797/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":"a45c4e50-94d5-46f8-bf1d-567622a3e479","owner":[],"postedDate":"January 3rd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-11T18:14:19+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-03 17:31:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3823797","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3823797","identity":"rs-3823797","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}