Lack of association between polymorphisms of catalase, copper-zinc superoxide dismutase (SOD), extracellular SOD and endothelial nitric oxide synthase genes and macroangiopathy in patients with type 2 diabetes mellitus

Objectives, The association between the polymorphisms of three different an tioxidative enzyme catalase, copper-zinc superoxide dismutase (Cu/Zn-SOD) a nd extracellular superoxide dismutase (EC-SOD)-genes and macroangiopathy wa s examined in patients with type 2 diabetes mellitus. The prevalence of the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and its association with macroangiopathy were also determined. Design. Cross-sectional study. Setting. District around Oulu University Hospital, North Finland. Subjects and methods. A total of 239 patients with type 2 diabetes mellitus and 245 control subjects were screened. Genotypes were determined by polym erase chain reaction (PCR) technique. The diagnosis of coronary heart disea se (CHD) was based on clinical and ECG criteria. The prevalences of cerebro vascular (CVD) and peripheral vascular diseases (PVD) were assessed on the basis of clinical criteria, Laboratory analyses were carried out in the hos pital laboratory. Results. No differences in the genotype distributions and allele frequencie s of the antioxidative enzymes were found between type 2 diabetes mellitus patients and controls. The eNOS genotypes and allele frequencies were also similar in the diabetic patients and controls being close to that reported earlier in the British population None of the polymorphisms were associated with macro- or microangiopathy or hypertension. However, male diabetic pat ients with eNOS Asp298Asp genotype had higher plasma very; low density lipo protein (VLDL) cholesterol and VLDL-triglyceride concentrations than those with the genotypes Glu298Glu or Glu298Asp (P < 0.01 for trend). Conclusions. The polymorphism of catalase, Cu/Zn SOD and EC-SOD genes were not related to cardiovascular disease in type 2 diabetes mellitus patients. The eNOS Glu298Asp variant was associated with plasma VLDL-containing lipo proteins but not with macroangiopathy in diabetic male patients. The findin gs do not support the notion that the polymorphisms of the key antioxidativ e enzymes could be amongst the factors that explain the high prevalence of macroangiopathy in patients with type 2 diabetes mellitus.