Abstract
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 (+Leprdb/+Leprdb, 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; p = 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.
Highlights
Type 2 diabetes (T2D) is a chronic metabolic disorder with a multifactorial pathogenesis
We evaluated the respective effects of three single nucleotide polymorphisms (SNPs) located in the Cholesteryl ester transfer protein (CETP) promoter region—rs3764261, rs4783961, and rs1800775—and a missense coding SNP of the CETP gene on the following: lipid concentrations, associated risk of T2D, and the specific complications of diabetic kidney disease (DKD) and diabetic retinopathy (DR) in a Taiwanese population
Non-diabetic controls were significantly younger in age at the time of the study and displayed lower hemoglobin A1C (HbA1C) levels, lower body mass index (BMI) levels, lower systolic and diastolic blood pressure, lower waist–hip ratio, higher total cholesterol, higher high-density lipoprotein cholesterol (HDL-C), lower low-density lipoprotein cholesterol (LDL-C), lower triglycerides, and higher estimated glomerular filtration rate (eGFR) levels than did the T2D patients
Summary
Type 2 diabetes (T2D) is a chronic metabolic disorder with a multifactorial pathogenesis. T2D involves complex interactions between environmental factors and genetic predisposition [1,2]. Macroand microvascular diseases are devastating complications of diabetes and are the major causes of morbidity and early mortality in diabetic individuals [3]. Dyslipidemia is regarded as an important risk factor for cardiovascular disease due to its influence on atherosclerosis and is considered to be a major complication and a leading cause of mortality in T2D patients [4]. The characteristics of diabetic dyslipidemia include high serum triglyceride concentrations, low serum high-density lipoprotein cholesterol (HDL-C) levels, and elevated low-density lipoprotein cholesterol (LDL-C) levels. Low levels of HDL-C were associated with an increased risk of T2D [5,6]. Factors reported determining HDL-C levels include hormonal, environmental, cultural, and regulatory genetic factors [7].
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