XbaI Polymorphisms Research Articles

Association of the ESR1 polymorphism with menopause and MLXIPL genetic variant influence serum uric acid levels in Slovak midlife women.

This study examines associations between the ESR1 (XbaI, PvuII) and the MLXIPL (rs3812316) gene polymorphisms, and uric acid (UA) levels in Slovak midlife women, subdivided according to their menopause status. We assessed a total of 362 women from 38 to 65 years of age. Women were recruited from different localities in the western and middle parts of Slovakia. Participants were interviewed during their medical examination at local health centers. They were investigated with respect to a variety of aspects such as medical, anthropometrical, and lifestyle. Participants provided a blood sample for biochemical analyses and DNA genotyping. The MLXIPL gene (rs3812316 SNP variant) and ESR1 gene (PvuII and XbaI) genotypes were then detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Data were analyzed using general linear models and multiple linear regression analyses to adjust for risk factors elevating the UA level such as fat mass (FM), triglycerides (TGs) and creatinine. A positive association between MLXIPL and UA level was observed in the total sample of women after control for confounding covariates, including FM, TGs, and creatinine (P = 0.027). Women with the CC genotype had higher UA levels than the G-allele carriers (261.5 μmol/L ± 68.3 vs 241.1 μmol/L ± 55.1 P = 0.013). A statistically significant association was noticed between postmenopause status and the ESR1 XbaI genotype and their effect on UA (P = 0.028). The Bonferroni pairwise comparison determined that the G-allele carriers in the postmenopausal period had higher estimated UA marginal mean (269.7 μmol/L) than the AA-allele postmenopausal women (236.5 μmol/L) (P = 0.012). The estimated UA marginal mean showed a significant increasing trend according to the MS in G allele carriers (248.5 μmol/L in pre/peri-menopausal vs 269.7 μmol/L in postmenopausal, P = 0.009). In contrast, a decreasing trend was observed in AA carriers (250.6 μmol/L in pre/perimenopausal women vs 236.5 μmol/L in postmenopausal). However, this trend was not statistically significant (P = 0.288). This cross-sectional study suggests that MLXIPL (rs3812316) polymorphism is associated with higher serum UA levels and that the ESR1 (XbaI) polymorphism is associated with UA levels only in the postmenopausal cohort.

Estrogen receptor 1 gene polymorphisms (PvuII and XbaI) are associated with type 2 diabetes in Palestinian women.

BackgroundType 2 diabetes mellitus (T2DM) is a multifactorial disease where both genetic and environmental factors contribute to its pathogenesis. The PvuII and XbaI polymorphisms of the estrogen receptor 1 (ESR1) gene have been variably associated with T2DM in several populations. This association has not been studied in the Palestinian population. Therefore, the aim of this study was to investigate the association between the PvuII and XbaI variants in the ESR1 and T2DM and its related metabolic traits among Palestinian women.MethodsThis case–control study included 102 T2DM and 112 controls in which PvuII and XbaI variants of the ESR1 gene were genotyped using amplicon based next generation sequencing (NGS).ResultsAllele frequencies of both PvuII and XbaI variants were not significantly different between patients and control subjects (P > 0.05). In logestic regression analysis adjusted for age and BMI, the ESR1 PvuII variant was associated with risk of T2DM in three genotypic models (P < 0.025) but the strongest association was observed under over-dominant model (TT+CC vs. TC) (OR = 2.32, CI [1.18–4.55] adjusted P = 0.013). A similar but non-significant trend was also observed for the ESR1 XbaI variant under the over-dominant model (AA+GG vs. AG) (OR = 2.03, CI [1.05–3.95]; adjusted P = 0.035). The frequencies of the four haplotypes (TA, CG, CA, TG) were not significantly different in the T2DM patients compared with control group (P > 0.025). Among diabetic group, an inverse trend with risk of cardio vascular diseases was shown in carriers of CG haplotype compared to those with TA haplotype (OR = 0.28, CI [0.09–0.90]; adjusted P = 0.035). Further, stratified analyses based on ESR1 PvuII and XbaI genotypes revealed no evidence for association with lipid levels (TC, TG, HDL, LDL).ConclusionsThis is the first Palestinian study to conclude that ESR1 PuvII and XbaI variants may contribute to diabetes susceptibility in Palestinian women. Identification of genetic risk markers can be used in defining high risk subjects and in prevention trials.

Estrogen receptor α and β gene polymorphism in relation to bone mineral density and lipid profile in Northeast Indian women

Estrogen regulates bone homeostasis and has a cardio-protective effect. Its physiological functions are mediated through receptors (ER) whose expression can be regulated by presence or absence of polymorphisms. However, the association between ER polymorphisms and BMD as well as lipids are inconsistent. The aim of the study was to investigate whether polymorphisms in ESR are associated with bone mineral density (BMD) and lipids in a cohort of Indian women. We studied PvuII, XbaI polymorphisms in ESR1 and AluI, RsaI polymorphisms in ESR2 genes and their association with bone mineral density (BMD) and lipids in premenopausal (n = 293, mean age: 33.01 ± 5.23 years) and postmenopausal (n = 145, mean age: 56.91 ± 7.1 years) women from Northeast India. AluI and RsaI polymorphisms in ESR2 gene were associated with BMD in postmenopausal women. Logistic regression analysis adjusted for age, BMI, tobacco and alcohol consumption revealed that xx genotype in XbaI polymorphism is associated with osteopenia at spine (OR = 3.3, 95% CI = 1.067–10.204) in postmenopausal women suggesting that allele X is protective (OR = 0.419, 95% CI = 0.177–0.991). Genotype aa in AluI polymorphism, seemed to be protective (OR = 0.092 for osteopenia; OR = 0.152 for osteoporosis) at spine whereas A allele was associated with osteopenia at femur (OR = 2.123, 95% CI = 1.079–4.166) in postmenopausal women. Allele r of RsaI polymorphism, was associated with osteoporosis at spine (OR = 3.222, 95% CI = 1.302–7.96). Thus, AIuI polymorphism of ESR2 gene was associated with spinal and femoral BMD whereas RsaI only with spinal BMD in postmenopausal women and ESR genotypes were not associated with lipids.

Association of GLUT-1 (XbaI) Gene Polymorphism in Diabetes and Diabetes Nephropathy Patients of North Indian Population

Diabetic nephropathy (DN) is a chronic complication of both type 1 and type 2 diabetes. However, there is still inadequate understanding of the exact mechanism related to progressive diabetic renal disease. The GLUT-1 XbaI gene polymorphism in the glucose transporter has been suggested in the development of DN. However, its association with T2DM and DN is controversial and has not been established in different ethnic populations. To enhance the understanding of GLUT-1 XbaI gene polymorphism in the context of T2DM and DN. We investigated the possible genetic association of GLUT-1 XbaI polymorphism with T2DM and DN in North Indian population. 100 T2DM patients and 100 patients of DN with 100 healthy controls were included in the study. GLUT-1 XbaI polymorphism was determined by PCR (polymerase chain reaction) and RFLP (restriction fragment length polymorphism). The obtained data showed no significant association between GLUT-1 XbaI gene polymorphism with T2DM and DN leading us to conclude that GLUT-1 XbaI gene polymorphism may not have major effects on T2DM and DN in North Indian population.

Association of Common Single Nucleotide Polymorphisms of Candidate Genes with Gallstone Disease: A Meta-Analysis.

Numerous studies have investigated the relationship between various candidate gene polymorphisms and gallbladder stone disease (GSD) across ethnic populations; however, the results are often inconsistent. This meta-analysis aims to comprehensively evaluate the influence of common ABCG8 T400K, ABCG8 D19H, ABCG8 C54Y, ApoB100 EcoRI, ApoB100 XbaI, ApoE HhaI, CETP TaqI, CYP7A1 Bsa, LRPAP1 I/D and TNF-α A308G polymorphisms on the risk of gallbladder stone disease. 33 Full-text articles with 9250 cases and 12,029 healthy controls (total 21,279 subjects) were analyzed using the RevMan software (V5.1) and the Comprehensive Meta-analysis software (Version 2.0, BIOSTAT, Englewood, NJ) a Random-effects model was applied. Begg's funnel plots, Fail-safe number, Egger's regression intercept and Begg and Mazumdar rank correlation tests were performed for the potential publication bias and sensitivity analysis. The studies were also sub-grouped into European and non-European groups to find out role of ethnicity, if any, on GSD risk. Studies included in quantitative synthesis were ABCG8 T400K rs4148217 (cases/controls, n = 671/1416) (4 studies), ABCG8 D19H rs11887534 (n = 1633/2306) (8 studies), ABCG8 C54Y rs4148211 (n = 445/1194) (3 studies), ApoB100 EcoRI rs1042031 (n = 503/390) (4 studies), ApoB100 XbaI rs693 (n = 1214/1389) (9 studies), ApoE HhaI rs429358 (n = 1335/1482) (12 studies), CETP TaqI rs708272 (n = 1038/1025) (5 studies), CYP7A1 Bsa rs3808607 (n = 565/514) (3 studies), LRPAP1 I/D rs11267919 (n = 849/900) (3 studies), TNF-α A308G rs1800629 (n = 997/1413) (3 studies). The combined results displayed significant association of ABCG8 D19H (GC + CC) [OR with 95%CI = 2.2(1.7-2.8); p < 0.00001], ABCG8 Y54C (GA + GG) [OR with 95%CI = 0.65(0.5-0.9); p = 0.01]. APOB100 EcoRI (GG vs. AA) [OR with 95%CI = 0.51(0.3-0.9); p = 0.05], (GG vs. GA) [OR with 95%CI = 0.6(0.4-0.9); p = 0.04], (GA + AA) [OR with 95%CI = 0.6(0.4-0.9); p = 0.006]. APOB Xba I (X- vs. X+) [OR with 95%CI = 0.53(0.3-0.8); p = 0.006. APOE Hha I (E4/E4 vs. E3/E3) [OR with 95%CI = 3.5(1.1-14.9); p = 0.04] and LRPAP1 I/D (ID + II) [OR with 95%CI = 1.27(1.0-1.6); p = 0.03] with the GSD risk. It was found that ABCG D19H was significantly associated with GSD in both European and Non-European populations. While APOB XbaI and LRPAP1 I/D markers were associated with gallstone disease only in Non- European population. Additionally, APOE HhaI and APOB 100 ECoRI were found to be associated with GSD only in European population. The results of quantitative synthesis suggest that the ABCG8 D19H polymorphism was associated with the increased risk of GSD in both European and Non-European populations, APOE Hha I and LRPAP1 I/D polymorphisms were associated with the increased risk of GSD in European and Non-European population respectively. However, no association was found in ABCG8 T400K, CETP Taq1, CYP7A1 Bsa and TNF-A308G polymorphisms with Gallstone Disease.

Clinical Importance of Estrogen Receptor 1 (ESR1) Gene Polymorphisms and Their Expression Patterns in Coronary Artery Disease Patients: A Study from India.

The influence of Estrogen Receptor 1 (ESR1) gene -397T>C (PvuII) and -351A>G (XbaI) polymorphisms on the risk of development of coronary artery disease (CAD) in the north Indian population was analysed. We hypothesized that ESR1 gene polymorphisms may influence the susceptibility to CAD through variation in Estrogen Receptor α (ERα) expression. To assess this concept, we evaluated ERα mRNA expression in blood plasma of CAD patients. The study included hundred CAD patients who showed presence of greater than 50% luminal stenosis in at least one major coronary artery in angiography along with hundred age and sex matched healthy controls. The ESR1 polymorphisms were investigated by PCR-RFLP. Quantitative Real Time PCR was carried out for the measurement of ERα mRNA expression. The results showed that genotypic frequencies of ESR1 -397T>C and -351A>G gene polymorphisms were significantly higher in CAD patients than control subjects (p < 0.0001). A significantly increased CAD risk was also found in dominant and codominant inheritance model for both of the SNPs. In gender based analysis these findings were replicated only in male subgroup. In case of -397T>C polymorphism, the ERα mRNA expression was highest in CAD patients with wild type homozygous TT genotype (2-∆ct = 0.28). A mutant 'C' allele, dose dependent, significant decrease in trend in ERα mRNA expression was observed, with lowest expression in mutant homozygous CC genotype (2-∆ct = 0.09), and intermediate expression level in heterozygous TC genotype (2-∆ct = 0.14) subgroups of CAD patients. In conclusion, this study demonstrates a significantly heightened risk of CAD associated with the inheritance of mutant genotypes of ESR1 -397T>C and -351A>G gene polymorphisms, in the north Indian population. This is the first report of a lowered ERα mRNA expression in conjunction with the presence of mutant 'C' allele of ESR1 -397T>C polymorphism with consequent increased CAD susceptibility.

Association between the estrogen receptor α gene polymorphisms rs2234693 and rs9340799 and severe and mild pre-eclampsia: a meta-analysis.

This meta-analysis was performed in order to determine the associations between the estrogen receptor α (ESR1) gene PvuII site (-397T/C, rs2234693) and XbaI site (-351A/G, rs9340799) polymorphisms with severe and mild pre-eclampsia. Eligible studies were identified by searching PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and WanFang databases until May 2018. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to calculate the associations. Six articles (consisting of seven studies; one article was considered as two separate studies with two different subpopulations) investigated the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms in severe and mild pre-eclampsia patients and included controls. The pooled results indicated an increased risk of severe pre-eclampsia for the XbaI -351A/G polymorphism (OR = 1.67, 95% CI = 1.10–2.25, P=0.017 for GG compared with AA+GA; OR = 1.81, 95% CI = 1.17–2.82, P=0.008 for GG compared with GA). The GG genotype of the ESR1 XbaI polymorphism could be a genetic risk factor for severe pre-eclampsia susceptibility. However, the ESR1 gene PvuII -397T/C polymorphism was not significantly associated with the risk of severe pre-eclampsia, and there was no association between mild pre-eclampsia and the ESR1 gene PvuII -397T/C and XbaI -351A/G polymorphisms separately. The current meta-analysis indicates that the ESR1 XbaI genetic polymorphism may be associated with severe pre-eclampsia. However, there was no association of the ESR1 gene PvuII and XbaI polymorphisms with the risk of mild pre-eclampsia. Owing to the low statistical power, the results may not be sufficiently robust and this conclusion should be interpreted cautiously, which highlights the requirement for large-scale and high-quality studies in this field.

Influence of Estrogen Receptor Alpha Polymorphism on Bone Mineral Density in Iranian Children

Background: Bone mass acquisition in childhood is directly linked to adult bone mineral density (BMD) and fracture risk. BMD is a heritable trait, more than 70% of its variability among a population is affected by genetic factors. Objectives: In the present study, we wanted to investigate the association between estrogen receptor alpha (ESR1) polymorphisms, PvuII (rs2234693) and XbaI (rs9340799), and bone area, bone mineral content (BMC), and BMD of the lumbar spine, femoral neck, and also of the total body less the head in Iranian children. Methods: The ESR1 gene PvuII and XbaI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Bone area, BMC, BMD, and bone mineral apparent density (BMAD) were assessed by dual-energy X-ray absorptiometry (DEXA). Linear regression was carried out to examine the effects of the ESR1 (PvuII and XbaI) polymorphisms on DEXA outputs when adjusted for confounding factors (i.e., age, sex, BMI, and pubertal stage) in 3 models. Results: ESR1 (PvuII) gene polymorphisms (CT vs. CC) showed significant effects on the BMC of the total body less the head in all 3 models. For ESR1 (XbaI), individuals with the AG genotype had higher lumbar spine BMD and lumbar spine BMAD compared to other genotypes. Conclusions: It seems that the PvuII and XbaI polymorphisms of ESR1 could be associated with BMC and BMD variation in Iranian children and adolescents.

ER\u03b1 PvuII and XbaI polymorphisms in postmenopausal women with posterior tibial tendon dysfunction: a case control study

BackgroundPosterior tibial tendon (PTT) insufficiency is considered as the main cause of adult acquired flat foot and is three times more frequent in females. High estrogen levels exert a positive effect on the overall collagen synthesis in tendons. We have previously demonstrated the association between some genetic single-nucleotide polymorphism (SNP) and tendinopathy. In the present study, we investigated the association of PvuII c454-397T>C (NCBI ID: rs2234693) and XbaI c454-351A>G (NCBI ID: rs9340799) SNPs in estrogen receptor alfa (ER-α) gene with PPT dysfunction.MethodsA total of 92 female subjects with PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) evidence of tendinopathy, were compared to 92 asymptomatic females who presented an intact PPT at MRI for PvuII and XbaI SNPs in the ER-α gene. Genomic DNA was extracted from saliva and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism.ResultsThe analysis of PvuII SNPs showed no significant differences in the frequency of alleles and genotypes between control and PTT dysfunction groups. The XbaI SNPs in the ER-α gene showed significant differences in the frequency of genotypes between control and test groups (p = 0.01; OR 95% 1.14 (0.55–2.33).ConclusionsThe XbaI SNP in the ERα gene may contribute to tendinopathy, and the A/A genotype could be a risk factor for PTT tendinopathy in this population. The PvuII SNP studied was not associated with PTT tendinopathy.

Estrogen receptor 1 gene polymorphisms are associated with metabolic syndrome in postmenopausal women in China

BackgroundMetabolic syndrome (MetS) includes obesity, diabetes, dyslipidemia and hypertension. Its incidence is rapidly increasing worldwide, particularly in postmenopausal women. Estrogens regulate glucose homeostasis and lipid metabolism via estrogen receptors 1 (ESR1) and 2 (ESR2). The current study aimed to elucidate associations of MetS with ESR1 and ESR2 gene polymorphisms in postmenopausal Chinese women.MethodsThis case-control study included 304 postmenopausal women (154 and 150 control and MetS patients, respectively). Clinical indicators related to MetS were assessed. Two ESR1 (PvuII and XbaI) and two ESR2 (RsaI and AluI) polymorphisms were evaluated by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis.ResultsESR1 polymorphisms were significantly different between MetS patients and healthy controls. G allele frequency for the XbaI polymorphism was significantly higher in patients than in control patients (p = 0.004, OR = 1.610, 95%CI 1.169–2.18). The haplotypes A–T (p = 0.015) and G–C (p = 0.024) showed significant differences. The minor alleles of the XbaI and PvuII gene polymorphisms in both homozygous and heterozygous forms showed associations with elevated waist circumference, fasting serum insulin and HOMA-IR. The minor G allele in homozygous and heterozygous forms of the RsaI and AluI gene polymorphisms showed associations with elevated total cholesterol and LDL-C.ConclusionsIn postmenopausal Chinese women, ESR1 polymorphism and the haplotypes A–T and G–C of XbaI–PvuII are associated with MetS, unlike ESR2 polymorphisms. Patients harboring the G allele of XbaI have elevated BMI, waist circumference, systolic and diastolic BP, FBG, HOMA-IR, total cholesterol, TG, LDL-C and NAFLD (%), and reduced HDL-C.

Association of Estrogen Receptor 1 Genetic Polymorphisms with Recurrent Spontaneous Abortion Risk.

Background:Estrogen is one of the most important reproductive steroidal hormones and plays a critical role in the maintenance of pregnancy, and its function is mediated by estrogen receptor 1(ESR1). The polymorphisms of ESR1 were involved in recurrent spontaneous abortion (RSA); however, the association between ESR1 polymorphisms and RSA remains controversial. The present meta-analysis was aimed to clarify the association between ESR1 PvuII (-397C/T, rs2234693) and XbaI (-351A/G, rs9340799) polymorphisms and the risk of RSA.Methods:All the included articles were retrieved from PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Med Online Database up to January 3, 2018. Data were processed in the Stata 12.0 software. The odds ratios (OR s) and 95% confidence intervals (95% CIs) were calculated using fixed-effects models (FEM)/random-effects models (REM).Results:Seven case–control studies with 836 cases and 1164 controls were included in the study. Generally, the ESR1 polymorphisms were not associated with RSA in any of the genetic analysis models. However, it was found that as rs9340799 polymorphism was related to increased risk of RSA in non-Asian group in the homozygous genetic model (OR = 2.40, 95% CI = 1.05–5.50, P = 0.039). Moreover, in Asian group, rs9340799 polymorphism was found to be related to decreased RSA risk in both the heterozygous model (OR = 0.53, 95% CI = 0.33–0.85, P = 0.009) and the dominant genetic model (OR = 0.55, 95% CI = 0.30–0.98, P = 0.042).Conclusions:Generally, there was no significant association between the polymorphisms of ESR1 and the risk of RSA. However, subgroup analysis indicated that ESR1 rs9340799 polymorphism was related to increased RSA risk in the non-Asian group while associated with decreased RSA risk in Asian group.

Associations of Estrogen Receptor Alpha Gene Polymorphisms with Type 2 Diabetes Mellitus and Metabolic Syndrome: A Systematic Review and Meta-Analysis.

The associations between PvuII (T>C) and XbaI (A>G) polymorphisms of estrogen receptor alpha (ESR1) gene with type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) are reported in many studies, but the results are inconsistent. This present work aims to assess the associations by performing a comprehensive meta-analysis. Relevant studies were searched through several databases. The pooled odd ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the associations of PvuII and XbaI polymorphisms with the risk of T2DM and MetS by using the STATA 14.0 software. Eight studies for T2DM and three articles about MetS were included in this meta-analysis. The overall results indicated that PvuII, rather than XbaI polymorphism, was associated with T2DM (regressive model: OR=0.673, 95% CI=0.550 to 0.823, praw<0.001, pFDR<0.003). The subgroup analysis based on race revealed an association of PvuII polymorphism with the decreased T2DM risk in Chinese population and a relationship between XbaI polymorphism and the reduced T2DM susceptibility in Caucasians. The difference of country may be one source of the heterogeneity for PvuII polymorphism and T2DM. However, neither PvuII nor XbaI polymorphism was related to the risk of MetS. The C allele of PvuII polymorphism presents a protective role in T2DM risk, especially in Chinese people. The G allele of XbaI polymorphism is related to a reduced risk for T2DM in Caucasian population. Nevertheless, neither of PvuII nor XbaI polymorphism is associated with MetS risk.

Analysis of the PvuII and XbaI polymorphisms in the estrogen receptor alpha gene in girls with central precocious puberty: a pilot study

BackgroundPrecocious puberty (PP) is defined as premature pubertal development. Its consequences surpass the physical evidence of sexual maturity with the premature epiphyseal closure of the long bones and the reduction of adult stature by varied degrees. Central PP is characteristically dependent on GnRH and most of its causes are not completely known. Altered estrogen action is also believed to be involved in the genesis of PP. In fact, estrogen receptor alpha (Rea) gene polymorphisms may be associated with early age at menarche. The objective of this study was to investigate the relationship between Reα gene polymorphisms (PvuII and XbaI) and the occurrence of central PP.MethodsA total of 73 girls with central PP and 101 girls with normal pubertal maturation were evaluated. Both groups were genotyped for the PvuII (T/C) and XbaI (A/G) polymorphisms in the Reα gene.ResultsThe frequency distribution of the XbaI (p = 0.28) and of the PvuII (p = 0.12) genotypes, as well as the XbaI and PvuII allelic variants (p = 0.23 and p = 0.86, respectively), did not differ between the groups.ConclusionThe PvuII and XbaI Rea gene polymorphisms do not appear to be related to development of central PP.

Estrogen receptor alpha XbaI polymorphism is associated with higher relaxin-3 levels in women with metabolic syndrome

Relaxin-3 is known to play a role in appetite regulation, increasing food intake and body weight. This study aimed to assess the relation of relaxin-3 with ERS1 XbaI and PvuII polymorphisms. One hundred female patients with metabolic syndrome were investigated. The genotypes of ESR1 XbaI and PvuII polymorphisms were assessed with PCR-RFLP. Serum relaxin-3 level was measured for all participants using ELISA. Higher relaxin-3 levels showed association with the minor GG genotype of ESR-1 XbaI polymorphism but not PvuII polymorphism.

Identification of XbaI polymorphism of the estrogen receptor alpha in mexicans at early posmenopause

INTRODUCTIONMenopause is the cessation of menstrual cycle, is diagnosed after at least twelve consecutive months whitout bleeding, it occurs due to the reduced functioning of the ovaries, resulting in lower levels of ovarian hormones primarily estradiol (NAMS, 2012). Estrogen suppression has been correlated with higher incidence of cardiovascular and metabolic diseases observed in this age group.Estrogens exert its actions through their receptors, the most studied isoforms of these receptors are: the alpha (ER‐α), beta (Er‐β) and the a G coupled (GPR30). Due to its action and location, an important role in the preservation of cardiovascular and metabolic health has been attributed to ER‐ α (Raushember y Cols, 2016).Several ER‐α polymorphisms have been described, one of the most interesting due to its association with the etiology of cardiovascular pathologies, is the termed as XbaI (rs9340799A&gt; G). This one, consists in the change of an adenine for a guanine, which modifies the affinity of the receptor for its ligand. The X allele has been linked to increased risk of bone demineralization, dyslipidemia, high body mass index (BMI), and oncologic diseases, such as breast cancer and ovarian tumors (chedrahui y Cols,2014; Lobo y Cols, 2014).The aim of this study was to identify the genotype of XbaI polymorphism in mexican posmenopausal women.MATERIALS AND METHODSA descriptive, observational, prospective, transversal, cohort study was carried out in 87 early posmenopausal women who attend to the climacteric clinic of “Hospital general Ignacio Zaragoza”. Clinical data, hormonal profile, blood pressure, antropometric parameters were evaluated. XbaI polymorphism was identified by restriction fragment length polymorphism (RFPL) method.RESULTSThe mean age was 53.01±5.08 years, the BMI average was 28.77±3.88 m/kg2. The averages of systolic, diastolic, and mean blood pressure were 116±10.44 mmHg, 78.7±9.39mmHg y 91.58±9.1 mmHg, respectively;27 patients had hypertension diagnostic under pharmacological treatment.We found 58.87%, 29.89% and 19.24% for xx, Xx and XX genotypes respectively (Graph 1).The averages of systolic, diastolic, mean blood pressure and BMI according XbaI genotype are showed in table 1, there was no statistical differences between groups.CONCLUSIONThe most common genotype in mexican posmenopausal women was xx.There was no differences in blood pressure and BMI according genotype.All patients had elevated values for BMI, independently of her XbaI genotypesSupport or Funding InformationnoneThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A multifactor dimensionality reduction model of gene polymorphisms and an environmental interaction analysis in type 2 diabetes mellitus study among Punjabi, a North India population

The effects of any single genetic variation for a common complex disease such as T2DM may be dependent on other genetic variations (gene-gene interactions) and environmental factors (gene-environment interactions). Multifactor Dimensionality Reduction (MDR) method helps in detection and characterization of susceptibility in common complex multifactor disorders like Type 2 Diabetes Mellitus (T2DM). The negligible studies are available with this model approach to detect the status of T2DM in north Indian population. Hence, the major objectives of the present study were to investigate the association of ENPP1 K121Q (rs1044498), TCF7L2 G > T (rs12255372) and GYS1 XbaI (A1 > A2) (rs8103451) gene variants with T2DM in the north Indian population; and to determine whether significant gene-gene and gene-environment (risk factors related to obesity and cardiovascular diseases) interactions exist between these selected genes in affecting type 2 diabetes mellitus using MDR analysis. A total of 500 participants consisting of 250 type 2 diabetes mellitus (T2DM) and 250 healthy subjects were recruited for this study. Genotyping was performed by PCR-RFLP method. Anthropometric and physiometric variables such as height, weight, waist circumference (WC), hip circumference (HC), SBP and DBP, were measured using standard protocol. The odds ratio and Hardy- Weinberg equilibrium deviation analyses were performed. The gene-gene and gene-environment interactions were performed by multifactor dimensionality reduction (MDR) analysis. In results it was observed that two genes ENPP1 and TCF7L2 are associated with T2DM. However, an insignificant association of the XbaI (A1 > A2) polymorphism in GYS1 gene with T2DM was demonstrated. The gene-gene interactions revealed that all the three SNPs have a synergistic effect with each other. The MDR method for gene-environment interactions showed all interaction models first to ninth order interactions for T2DM patients as significant for susceptibility of obesity. The results showed that both the genes ENPP1 and TCF7L2 interacting with WHR and WC increase the susceptibility of obesity many folds among T2DM patients and non-diabetic controls. In conclusion, it is suggested that pathogenesis of T2DM, obesity and hypertension involves interplay of a variety of susceptibility alleles and environment. The gene-gene and gene-environment interactions are not only possible, but, are probably ubiquitous in determining the susceptibility of complex human diseases. Further studies on epistatic interactions are warranted to elucidate their possible underlying role in pathogenesis of T2DM.

Association between ERα polymorphisms and systemic lupus erythematosus: susceptibility and in silico analysis.

Systemic lupus erythematous (SLE) is a multisystem and autoimmune disorder leading to damage of multi-organ systems. The current study aimed to assess the possible association between ERα gene polymorphisms and SLE in a southeast Iranian population. The ERα PvuII and XbaI polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in 170 SLE patients and 186 healthy subjects. There was no association between ERα PvuII and XbaI polymorphisms and SLE susceptibility; however, the combination of the TC/AA and CC/GG genotypes of ESR α PvuII and XbaI polymorphisms were more frequent in SLE patients. The results indicated that TT haplotype of the ERα gene polymorphisms could increase the SLE risk almost 2.4-fold (odds ratio 2.4, 95% CI 1.3-4.3, P=0.005). The in silico analysis revealed that the ERα PvuII and XbaI single nucleotide polymorphisms occurred in acceptor splicing sites, and these mutations can lead to the increase of Human Splicing Finder score of the mutant alleles. The ESR α PvuII and XbaI polymorphisms have no association with SLE; however, the combination of the TC/AA and CC/GG genotypes were associated with SLE susceptibility.

Niveles de estradiol en niños y jóvenes y su relación con género, edad, presión arterial, lípidos plasmáticos y polimorfismo XbaI del receptor de estrógenos.

La identificación de factores de riesgo para las enfermedades cardiovasculares (ECV) puede ayudar a prevenir su desarrollo. Las hormonas esteroides a través de sus receptores y las variaciones genéticas influyen sobre el metabolismo de los lípidos y la presión arterial, entre otras funciones. Métodos: Estudio descriptivo realizado en niños y adolescentes entre 8 y 18 años de edad. Objetivo: Determinar los niveles de estradiol y su relación con género, edad, presión arterial, lípidos plasmáticos y polimorfismo XbaI del receptor de estrógenos. Resultados: No se encontró relación estadística entre el polimorfismo XbaI y las concentraciones de estradiol, pero sí entre el polimorfismo y el perfil lipídico, de igual manera entre las concentraciones de esta hormona con triglicéridos y c-VLDL. Conclusión: Este trabajo evidencia la relación entre niveles de estrógenos, edad, presión sanguínea y lípidos plasmáticos, de igual forma demuestra una relación entre polimorfismo XbaI del ESR1 y los niveles de lípidos.

No Association of Genetic Markers with Carotid Intimal Medial Thickness in β-Thalassemia Major Patients

Regular transfusion leads to cardiac siderosis resulting in cardiac complications that account for more than 71% of the total mortality in thalassemia patients. We aimed to study the variants of matrix metalloproteinase-9 (MMP9), matrix Gla protein (MGP), and estrogen receptor α(ERα), which might be contributing to atherosclerosis, leading to heart failure in thalassemia major. One hundred and five thalassemia patients on regular transfusion and iron chelation therapy were enrolled for the study. Carotid artery intimal medial thickness (CIMT) measurement was done to check for atherosclerosis. MMP 9 (C1562T), MGP (T138C), and ER α gene ( Pvu II (rs2234693T > C) and Xba I (rs9340799A > G) polymorphism were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. CIMT values were within the normal range (<0.90 mm) in all patients. There was no difference in mean CIMT values between males and females (0.56 ± 0.11 versus 0.56 ± 0.12, p = 0.928). There was no correlation of CIMT with age, body surface area, and body mass index as well as with serum ferritin levels. No statistically significant difference in frequency of MMP9, MGP, and ERα genotypes was seen in two dichotomized groups of CIMT (CIMT < 0.56 and CIMT ≥ 0.56). Variants of MMP9 , MGP , and ERα have a reserved influence on cardiac disease pathogenesis, and the disease phenotype in thalassemia patients may be more strongly impacted by other factors.

HUBUNGAN POLIMORFISME GEN RESEPTOR ESTROGEN ALFA DENGAN JUMLAH SEL T CD4+ PADA ANAK TERINFEKSI HIV

Background: Estrogen plays a key role in human physiological processes. Polymorphisms of estrogen receptors have been implicated in the development of numerous diseases. The aim of this study was to evaluate the frequency of ERα gene Pvull and Xbal polymorphisms and assessing their association with CD4+ T-cell counts in HIV-infected children on highly active antiretroviral therapy.Methods: CD4+ T cell counts were determined using the FACS count system. ERα PvuII and XbaI polymorphisms were analyzed by PCR-RFLP.Results: This study enrolled 34 HIV-infected children on HAART. The frequencies of the PvuII and XbaI gene polymorphisms were PP 41,2%, Pp 26,5%, pp 32,4% and XX 35,3%, Xx 17,6%, xx 47,1% respectively. CD4+ T-cell counts were significantly associated with XbaI polymorphisms (p&lt;0.05), but not PvuII polymorphisms (p&gt;0.01).Discussion: Host genetic factor polymorphism is an important determinant of HIV disease progression and treatment response. The ERα Pvull and Xbal polymorphisms can increase risk for the development of HIV-related complication,including oral diseases.Conclusion: The ERα gene XbaI polymorphism was significantly associated with CD4+ T-cell counts. It may explain the role of estrogen in the regulation of HIV replication. Studying human genetic variation in HIV-infected individuals is important to guide a new therapeutic approach.