Ereqat Suheir, Cauchi Stéphane, Eweidat Khaled, Elqadi Muawiyah, Nasereddin Abedelmajeed
Biochemistry and Molecular Biology Department-Faculty of Medicine, Al-Quds University, East Jerusalem, Palestine.
CNRS, UMR8204, Lille, France.
PeerJ. 2019 Jun 28;7:e7164. doi: 10.7717/peerj.7164. eCollection 2019.
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 and T2DM and its related metabolic traits among Palestinian women.
This case-control study included 102 T2DM and 112 controls in which PvuII and XbaI variants of the gene were genotyped using amplicon based next generation sequencing (NGS).
Allele frequencies of both PvuII and XbaI variants were not significantly different between patients and control subjects ( > 0.05). In logestic regression analysis adjusted for age and BMI, the PvuII variant was associated with risk of T2DM in three genotypic models ( < 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 = 0.013). A similar but non-significant trend was also observed for the XbaI variant under the over-dominant model (AA+GG vs. AG) (OR = 2.03, CI [1.05-3.95]; adjusted = 0.035). The frequencies of the four haplotypes (TA, CG, CA, TG) were not significantly different in the T2DM patients compared with control group ( > 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 = 0.035). Further, stratified analyses based on PvuII and XbaI genotypes revealed no evidence for association with lipid levels (TC, TG, HDL, LDL).
This is the first Palestinian study to conclude that 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.
2型糖尿病（T2DM）是一种多因素疾病，遗传和环境因素均对其发病机制有影响。雌激素受体1（ESR1）基因的PvuII和XbaI多态性在多个人群中与T2DM的关联各不相同。在巴勒斯坦人群中尚未对这种关联进行研究。因此，本研究的目的是调查巴勒斯坦女性中ESR1基因的PvuII和XbaI变异与T2DM及其相关代谢特征之间的关联。
本病例对照研究纳入了102例T2DM患者和112例对照，采用基于扩增子的下一代测序（NGS）对ESR1基因的PvuII和XbaI变异进行基因分型。
患者和对照受试者之间PvuII和XbaI变异的等位基因频率无显著差异（P>0.05）。在根据年龄和BMI进行校正的逻辑回归分析中，ESR1基因的PvuII变异在三种基因型模型中与T2DM风险相关（P<0.025），但在超显性模型（TT+CC与TC相比）下观察到最强的关联（OR=2.32，CI[1.18 - 4.55]；校正后P=0.013）。在超显性模型（AA+GG与AG相比）下，ESR1基因的XbaI变异也观察到类似但不显著的趋势（OR=2.03，CI[1.05 - 3.95]；校正后P=0.035）。与对照组相比，T2DM患者中四种单倍型（TA、CG、CA、TG）的频率无显著差异（P>0.025）。在糖尿病组中，与TA单倍型携带者相比，CG单倍型携带者的心血管疾病风险呈相反趋势（OR=0.28，CI[0.09 - 0.90]；校正后P=0.035）。此外，基于ESR1基因的PvuII和XbaI基因型的分层分析未发现与血脂水平（总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白）相关的证据。
这是第一项巴勒斯坦研究，得出ESR1基因的PuvII和XbaI变异可能导致巴勒斯坦女性患糖尿病易感性的结论。识别遗传风险标志物可用于确定高危人群和预防试验。
