胆固醇酯转移蛋白基因变异与台湾人群 2 型糖尿病及糖尿病肾病发病风险的关系。
Cholesteryl Ester Transfer Protein Genetic Variants Associated with Risk for Type 2 Diabetes and Diabetic Kidney Disease in Taiwanese Population.
机构信息
School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
出版信息
Genes (Basel). 2019 Oct 8;10(10):782. doi: 10.3390/genes10100782.
Cholesteryl ester transfer protein (CETP) plays an important role in lipid metabolism. Low levels of high-density lipoprotein cholesterol (HDL-C) increase the risk of type 2 diabetes (T2D). This study investigated CETP gene variants to assess the risk of T2D and specific complications of diabetic kidney disease (DKD) and diabetic retinopathy. Towards this, a total of 3023 Taiwanese individuals (1383 without T2D, 1640 with T2D) were enrolled in this study. T2D mice (+Lepr/+Lepr, db/db) were used to determine CETP expression in tissues. The A-alleles of rs3764261, rs4783961, and rs1800775 variants were found to be independently associated with 2.86, 1.71, and 0.91 mg/dL increase in HDL-C per allele, respectively. In addition, the A-allele of rs4783961 was significantly associated with a reduced T2D risk (odds ratio (OR), 0.82; 95% confidence interval (CI), 0.71‒0.96)), and the A-allele of rs1800775 was significantly related to a lowered DKD risk (OR, 0.78; 95% CI, 0.64‒0.96). CETP expression was significantly decreased in the T2D mice kidney compared to that in the control mice (T2D mice, 0.16 0.01 vs. control mice, 0.21 0.02; = 0.02). These collective findings indicate that CETP variants in the promoter region may affect HDL-C levels. Taiwanese individuals possessing an allele associated with higher HDL-C levels had a lower risk of T2D and DKD.
胆固醇酯转移蛋白（CETP）在脂质代谢中发挥重要作用。高密度脂蛋白胆固醇（HDL-C）水平低会增加 2 型糖尿病（T2D）的风险。本研究调查了 CETP 基因变异，以评估 T2D 及糖尿病肾病（DKD）和糖尿病视网膜病变等特定并发症的风险。为此，共纳入 3023 名台湾个体（1383 名无 T2D，1640 名有 T2D）。使用 T2D 小鼠（+Lepr/+Lepr，db/db）来确定组织中的 CETP 表达。rs3764261、rs4783961 和 rs1800775 变体的 A 等位基因与 HDL-C 每等位基因分别增加 2.86、1.71 和 0.91mg/dL 独立相关。此外，rs4783961 的 A 等位基因与 T2D 风险降低显著相关（比值比（OR），0.82；95%置信区间（CI），0.71‒0.96），rs1800775 的 A 等位基因与 DKD 风险降低显著相关（OR，0.78；95%CI，0.64‒0.96）。与对照组相比，T2D 小鼠肾脏的 CETP 表达显著降低（T2D 小鼠，0.16 0.01 对 对照组，0.21 0.02；=0.02）。这些研究结果表明，启动子区域的 CETP 变异可能会影响 HDL-C 水平。携带与更高 HDL-C 水平相关等位基因的台湾个体患 T2D 和 DKD 的风险较低。
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