The relationship between diabetic macroangiopathy or microangiopathy and apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising consecutive patients with poor diabetic control (HBA1 13.2% +/- 2.7 (SD)) referred to our hospital. Plasma cholesterol and triglyceride concentrations were higher in the patients who were homozygous for the X2 allele (presence of XbaI cleavage site). Patients with the X1 allele (absence of XbaI cleavage site) tended to have a higher frequency of macroangiopathy, although the differences were not statistically significant. There was no difference in the prevalence of microangiopathy between the groups. In subjects with only an R1 allele (= R+; homozygous for the presence of EcoRI cleavage site) the prevalence of coronary heart disease (CHD) was observed to be high (61.9%) as compared to the subjects possessing an R2 allele (= R-; homozygous or heterozygous for the absence of the EcoRI cleavage site) (46.7%; p
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
The exon 16 of the cholesteryl ester transfer protein (CETP) gene was screened for possible mutations in patients with low plasma high-density lipoprotein cholesterol (HDL-C) levels and established coronary heart disease. 115 men who had undergone coronary bypass surgery were compared with a random population sample of 515 subjects. A single G to A substitution at base pair 1696 was found in the 3' untranslated region of the CETP gene. Among the patients with low HDL-C, the plasma CETP activity was 29% lower (P = 0.002) in the subjects homozygous for the mutation than in those with other genotypes. The same effect was observed in the random population sample (P = 0.02). The mutation did not affect the plasma lipid or lipoprotein values, although the mean HDL-C tended to be slightly higher and the ratio of cholesterol content in the apo B-containing lipoproteins to HDL-C slightly lower in the homozygotes compared with the other genotypes. In conclusion, we describe a prevalent mutation at the CETP gene locus associated with low plasma CETP activity. Our results support previous findings suggesting that the genes in chromosome 16 may be important in the regulation of reverse cholesterol transport and in protection against coronary heart disease.