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

Abstract

Background Type 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. Methods This 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). Results Allele 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). Conclusions This 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.

Functionally significant polymorphisms of ESR1and PGR and risk of intrauterine growth restriction in population of Central Russia

“…Previously, loci rs2234693 and rs9340799 associated with IUGR were also reported as candidate for preeclampsia [28][29][30], age of menarche [31], precocious puberty [32], height at menarche [33], premature ovarian failure [34], endometriosis [35], breast cancer [36], type II diabetes mellitus [37]. Specifically, Molvarec [28] reported the GG genotype of the rs9340799 was associated with a lower risk of IUGR in patients with severe preeclampsia while the homozygous TA haplotype carriers of ESR1 rs2234693 and rs9340799 polymorphisms showed an increased risk of severe preeclampsia.…”

Studies on the Mechanism of Gegen Qinlian Decoction in Treating Diabetes Mellitus Based on Network Pharmacology

“…The 24 core genes were verified in the GEO database and existing literature studies. [46][47][48][49][50][51][52][53][54][55][56] As shown in Table 2, 12 of these genes were differentially expressed in GSE12643, GSE14887, GSE25724, GSE2956, and GSE65057 dataset. In the existing literature, another 12 genes were extensively related to the mechanism of diabetes mellitus.…”

Association of DNA methylation and genetic variations of the APOE gene with the risk of diabetic dyslipidemia

“…The DNA concentration was determined using a NanoDrop 1000 spectrophotometer (Thermo Fisher Scientific, Inc.) and was stored at -20˚C until required for further analysis. Amplicon-based next generation sequencing (NGS) was used for genotyping as previously described (18). Briefly, three primers (two forward and one reverse) were used in multiplex PCR to target the two SNPs of APOE rs429358 [C/T] and rs7412 [C/T].…”