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阿联酋2型糖尿病患者维生素D受体基因多态性

Vitamin D receptor gene polymorphisms among Emirati patients with type 2 diabetes mellitus.

作者信息

Safar Habiba Al, Chehadeh Sarah El Hajj, Abdel-Wareth Laila, Haq Afrozul, Jelinek Herbert F, ElGhazali Gehad, Anouti Fatme Al

机构信息

Faculty of Biomedical Engineering, Khalifa University of Science, Technology & Research, Abu Dhabi, United Arab Emirates; Khalifa University Center of Biotechnology, Abu Dhabi, United Arab Emirates.

Khalifa University Center of Biotechnology, Abu Dhabi, United Arab Emirates.

出版信息

J Steroid Biochem Mol Biol. 2018 Jan;175:119-124. doi: 10.1016/j.jsbmb.2017.03.012. Epub 2017 Mar 18.

Abstract

At a prevalence rate close to 19.5%, the UAE has one of the highest rates of Type 2 Diabetes Mellitus (T2DM) in the world. Genome wide association studies (GWAS) have led to the identification of several genetic variants that are associated with T2DM. Recently, genes involved in vitamin D metabolism have gained interest because of the association between vitamin D deficiency (VDD) and increased risk for T2DM. Among these, the Vitamin D receptor (VDR) gene is a good candidate for T2DM susceptibility. The aim of this study was to investigate the association between VDR polymorphisms and T2DM among a representative sample of the Emirati population. In this cross sectional study, two hundred and sixty four patients with T2DM and ninety-one healthy controls were enrolled. The study population was genotyped for the three VDR gene mutations, TaqI (rs731236), FokI (rs2228570) and BsmI (rs1544410). VDR alleles and haplotypes were compared between patients and their healthy controls. The mean age of the T2DM cohort was 60±11.59years and 48.21±12.17years for the healthy controls. The G-allele and GG genotype of rs2228570 and T-allele and TT genotype of rs1544410 SNPs were associated with T2DM. In regards to T2DM-related metabolic complications, the AG and GG genotypes of rs731236 were significantly associated with higher total cholesterol (p=0.011) and LDL-cholesterol (p=0.009) levels in the patients with T2DM. In contrast, the CT genotype of rs1544410 was significantly associated with lower BMI (p=0.031) and the TT genotype was associated with lower LDL-cholesterol level (p=0.007). The frequency of AAT and GGC haplotypes was also different between groups (p=0.014; p=0.032, respectively), implying that these haplotypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population. To conclude, an association between SNPs in the VDR gene (except for rs731236) and T2DM per se was demonstrated. The rs731236 variant was shown to be associated with high cholesterol and LDL-cholesterol levels in T2DM patients, while rs1544410 was associated with lower BMI and lower LDL cholesterol levels. Our results imply that alleles and haploypes of the VDR gene are associated with the susceptibility to T2DM in the Emirati population.

摘要

阿联酋2型糖尿病(T2DM)患病率接近19.5%,是世界上该疾病患病率最高的国家之一。全基因组关联研究(GWAS)已鉴定出多个与T2DM相关的基因变异。最近,由于维生素D缺乏(VDD)与T2DM风险增加之间的关联,参与维生素D代谢的基因受到关注。其中,维生素D受体(VDR)基因是T2DM易感性的一个良好候选基因。本研究的目的是在阿联酋人群的代表性样本中调查VDR基因多态性与T2DM之间的关联。在这项横断面研究中,纳入了264例T2DM患者和91例健康对照。对研究人群进行了三种VDR基因突变(TaqI(rs731236)、FokI(rs2228570)和BsmI(rs1544410))的基因分型。比较了患者及其健康对照之间的VDR等位基因和单倍型。T2DM队列的平均年龄为60±11.59岁,健康对照为48.21±12.17岁。rs2228570的G等位基因和GG基因型以及rs1544410单核苷酸多态性的T等位基因和TT基因型与T2DM相关。关于T2DM相关的代谢并发症,rs731236的AG和GG基因型与T2DM患者较高的总胆固醇(p=0.011)和低密度脂蛋白胆固醇(p=0.009)水平显著相关。相反,rs1544410的CT基因型与较低的体重指数(p=0.031)显著相关,TT基因型与较低的低密度脂蛋白胆固醇水平(p=0.007)相关。两组之间AAT和GGC单倍型的频率也不同(分别为p=0.014;p=0.032),这意味着VDR基因的这些单倍型与阿联酋人群对T2DM的易感性相关。总之,证明了VDR基因中的单核苷酸多态性(rs731236除外)与T2DM本身之间存在关联。rs731236变异体与T2DM患者的高胆固醇和低密度脂蛋白胆固醇水平相关,而rs1544410与较低的体重指数和较低的低密度脂蛋白胆固醇水平相关。我们的结果表明,VDR基因的等位基因和单倍型与阿联酋人群对T2DM的易感性相关。

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