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维生素 D 受体多态性对中国 2 型糖尿病易感性的影响:与高甘油三酯血症的相互作用。

The influence of VDR polymorphisms on the type 2 diabetes susceptibility in Chinese: an interaction with hypertriglyceridemia.

机构信息

Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan, China.

出版信息

Mol Genet Genomics. 2021 Jul;296(4):837-844. doi: 10.1007/s00438-021-01784-z. Epub 2021 Apr 20.

Abstract

Evidence shows that mutations in vitamin D receptor (VDR) have been linked with an increased risk of type 2 diabetes (T2D). However, the interaction effect between VDR variants and environmental factors on the T2D susceptibility remained unclear. Therefore, the current study was conducted to explore the joint effect of VDR polymorphisms and serum triglyceride level on T2D. A total of 2017 participants were included in the cross-sectional study. Taqman probe assays were applied to rs3847987 and rs739837 genotyping. Multiple logistic regression and general linear model were used to examine the effect of interaction between VDR variants and TG on T2D susceptibility and fasting serum glucose, respectively. The results showed that rs739837 polymorphism was significantly associated with an increased risk of T2D under the dominant model (OR = 1.30, 95% CI 1.02-1.66), after adjusting for potential risk factors. Meanwhile, there was a significant additive interaction between rs3847987 and hypertriglyceridemia (synergy index [SI]: 2.98, 95% CI: 1.23-7.23) and between rs739837 and hypertriglyceridemia (SI: 2.36, 95% CI: 1.05-5.31) on T2D susceptibility. Additionally, a significant linear association between fasting glucose and rs3847987 had been found at high triglyceride level (> 1.90 mmol/L) with an inversely concentration-dependent manner. The study provided further evidence that rs739837 and high level of triglyceride were both associated with higher T2D susceptibility in Chinese population. Additionally, the detrimental effect of VDR variants on T2D could be modified by hypertriglyceridemia status.

摘要

证据表明,维生素 D 受体 (VDR) 突变与 2 型糖尿病 (T2D) 的风险增加有关。然而,VDR 变体与环境因素对 T2D 易感性的相互作用影响仍不清楚。因此,本研究旨在探讨 VDR 多态性与血清甘油三酯水平对 T2D 的联合作用。共纳入 2017 名参与者进行横断面研究。应用 Taqman 探针法进行 rs3847987 和 rs739837 基因分型。采用多因素 logistic 回归和一般线性模型分别检验 VDR 变异与 TG 之间的交互作用对 T2D 易感性和空腹血糖的影响。结果显示,在调整了潜在危险因素后,rs739837 多态性在显性模型下与 T2D 风险增加显著相关(OR=1.30,95%CI 1.02-1.66)。同时,rs3847987 与高甘油三酯血症之间存在显著的相加交互作用(协同指数 [SI]:2.98,95%CI:1.23-7.23),rs739837 与高甘油三酯血症之间存在显著的相加交互作用(SI:2.36,95%CI:1.05-5.31)。此外,在高甘油三酯水平(>1.90mmol/L)下,空腹血糖与 rs3847987 之间存在显著的线性关联,且呈浓度依赖性的反比关系。本研究进一步证明,rs739837 和高水平甘油三酯在中国人群中均与更高的 T2D 易感性相关。此外,VDR 变异对 T2D 的有害影响可被高甘油三酯血症状态所修饰。

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