Genetics
CETP EcoNI genotype 2-2 predicts higher rates of coronary disease and neuropathy in type 2 diabetes (Clin Genet 1994)
Original title: DNA polymorphisms at the locus for human cholesteryl ester transfer protein (CETP) are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus
In 136 male and 122 female patients with non-insulin-dependent diabetes mellitus, the cholesteryl ester transfer protein (CETP) EcoNI genotype 2-2 was associated with more myocardial infarction (38% versus 18% for genotype 1-1, P < 0.02), more coronary heart disease overall (73% versus 52% for genotype 1-2, P < 0.02), and more neuropathy (31% versus 12-14% for genotypes 1-1 and 1-2, P < 0.02 or less). Coronary heart disease was more common in men with genotype 2-2 than genotype 1-1 (70% versus 42%, P < 0.05), while women showed no significant CHD difference between genotypes. Cerebrovascular disease was more prevalent with the TaqIB 1-1 genotype than 2-2 (21% versus 6%, P < 0.02). Apolipoprotein AI-CIII-AIV cluster polymorphisms showed no association with macroangiopathy risk.
Original abstract
The effect of variation at the cholesteryl ester transfer protein (CETP) gene locus and in the apolipoprotein (apo) AI-CIII-AIV gene cluster on the susceptibility of individuals with non-insulin-dependent diabetes mellitus (NIDDM) to atherosclerotic vascular disease was studied in 136 male and 122 female patients with NIDDM. The prevalence of myocardial infarction was high (38%) in patients with the EcoNI genotype 2-2 of the CETP gene locus (= 2-2; subjects homozygous for the absence of the restriction site) compared with patients with the genotype 1-1 (= 1-1; subjects homozygous for the presence of the restriction site) (18%, p < 0.02). The prevalence of any evidence of coronary heart disease (CHD) (presence of ischaemic ECG changes or definite myocardial infarction) was high in 2-2 (73%) compared with the genotype 1-2 (= 1-2; heterozygous for the presence of the restriction site) (52%, p < 0.02) and genotype 1-1 (p = 0.06). CHD was more prevalent in men with 2-2 (70%) than in those with 1-1 (42%, p < 0.05), but in women no significant differences were found in the prevalences of CHD between the EcoNI genotypes. Neuropathy was more often present in the patients with 2-2 (31%) than in those with 1-1 (12%, p < 0.02) or 1-2 (14%, p < 0.01). Plasma total cholesterol and total- and VLDL-triglycerides were higher in women with the EcoNI genotype 1-1 than in those with the genotype 1-2. In men no significant differences in plasma lipids were found. In addition, the prevalence of cerebrovascular disease was high (21%) in the patients with the genotype 1-1 of the TaqIB polymorphism compared with the genotype 2-2 (6%, p < 0.02). None of the alleles defined by four polymorphisms in the apo AI-CIII-AIV gene region were associated with an increased risk for macroangiopathy. The PstI polymorphism had an effect on plasma triglyceride levels. At the CETP locus one pair of loci (TaqIB and EcoNI) and three pairs of loci at the apo AI-CIII-AIV gene cluster (SacI and MspI, SacI and PvuII and MspI and PvuII) showed significant allelic association. In conclusion, the variation of CETP locus modulates the risk for diabetic complications in patients with NIDDM and the effect seems to be different between men and women. In contrast, the AI-CIII-AIV gene cluster polymorphisms seem not to be related to the risk of CHD in NIDDM.(ABSTRACT TRUNCATED AT 400 WORDS)
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.