VKORC1-1639G>A 多态性与 2 型糖尿病患者颈动脉内膜中层厚度的相关性。

Association of VKORC1 -1639 G>A polymorphism with carotid intima-media thickness in type 2 diabetes mellitus.

机构信息

Lab of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece.

出版信息

Diabetes Res Clin Pract. 2011 Nov;94(2):236-41. doi: 10.1016/j.diabres.2011.06.021. Epub 2011 Jul 20.

DOI:10.1016/j.diabres.2011.06.021

PMID:21767890

Abstract

AIMS

Media calcification is a predictor of cardiovascular mortality in type 2 diabetes mellitus (T2DM). Undercarboxylation of some vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can lead to calcification. We examined a potential association between VKORC1 -1639 G>A polymorphism and T2DM and, also, the association of this polymorphism with carotid intima-media thickness (cIMT).

METHODS

VKORC1 -1639 G>A polymorphism was determined in 299 T2DM patients and 328 controls of Caucasian origin using PCR-RFLP. cIMT was measured in a subgroup of 118 T2DM patients.

RESULTS

The frequency of VKORC1 genotypes between diabetic and nondiabetic subjects differed significantly (p=0.01). VKORC1 genotype was associated with T2DM in an adjusted model (OR 1.36, p=0.009). A statistically significant difference was observed in the maximum value of cIMT among different genotypes. VKORC1 -1639 G>A polymorphism was an independent predictor of cIMT (p=0.029) after adjusting for established risk factors.

CONCLUSIONS

The association between VKORC1 -1639 G>A polymorphism and risk of T2DM could be due to the higher prevalence of calcification in T2DM patients. This is supported by the independent association between VKORC1 -1639 G>A polymorphism and maximum cIMT in T2DM patients which is likely due to atherosclerosis characterized by increased calcification.

摘要

目的

在 2 型糖尿病（T2DM）患者中，血管钙化是心血管死亡率的预测因子。由于 VKORC1 的遗传多态性，一些维生素 K 依赖性蛋白的羧化不足，可能导致钙化。我们研究了 VKORC1-1639 G>A 多态性与 T2DM 之间的潜在关联，以及该多态性与颈动脉内膜中层厚度（cIMT）之间的关联。

方法

采用 PCR-RFLP 法检测 299 例 T2DM 患者和 328 例白种人对照组的 VKORC1-1639 G>A 多态性。在 118 例 T2DM 患者亚组中测量 cIMT。

结果

糖尿病患者和非糖尿病患者的 VKORC1 基因型频率差异有统计学意义（p=0.01）。在调整后的模型中，VKORC1 基因型与 T2DM 相关（OR 1.36，p=0.009）。不同基因型之间 cIMT 的最大值存在统计学差异。在调整了已建立的危险因素后，VKORC1-1639 G>A 多态性是 cIMT 的独立预测因子（p=0.029）。