Apolipoprotein B gene DNA polymorphisms are associated with macro‐ and microangiopathy in non‐insulin‐dependent diabetes mellitus

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Abstract
Ukkola O, Savolainen MJ, Salmela PI, von Dickhoff K, Kesäniemi YA. Apolipoprotein B gene DNA polymorphisms are associated with macro‐and microangiopathy in non‐insulin‐dependent diabetes mellitus.Clin Genet 1993: 44: 177–184. © Munksgaard, 1993The 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%\pm2.7 (SD)) referred to our hospital. Plasma cholesterol and triglyceride concentrations were higher in the patients who were homozygous for the X2 allele (presence of Xba I cleavage site). Patients with the X1 allele (absence of Xba I 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 EcoR I 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 EcoR I cleavage site) (46.7%; p<0.02). When the polymorphisms Xba I (subjects homozygous for the absence of the cutting site = X +; subjects homozygous or heterozygous for the presence of the cutting site = X —) and EcoR I were combined, the prevalence of macroangiopathy was observed to be high in X + R + (80.0%) as compared with X + R‐ (44.2%), X‐R+ (56.8%) and X‐R‐ (50.0%) (p<0.03). The prevalence of macroangiopathy tended to be particularly high in patients with the apoprotein E4 allele (phenotype E4\4 or E4/3), combined with either X+ or R +. Our findings suggest that variation at the apoB locus is one of the factors involved in predisposing diabetic patients to the development of arterial disease. As in previous studies the effect of the variation at the apoB gene on circulating lipid levels was observed. The data also support a role for the e4 allele of the apolipoprotein E gene as an important determinant of macroangiopathy in NIDDM.