INSULIN-RECEPTOR SUBSTRATE-1 GENE POLYMORPHISM AND CARDIOVASCULAR RISK IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS AND PATIENTS UNDERGOING CORONARY ANGIOGRAPHY

Clustering of risk factors for cardiovascular disease related to insul in resistance may account for the increased incidence of vascular dise ase in these conditions and in non-diabetic subjects, To investigate t he relationship between a coding polymorphism in the insulin receptor substrate-1 gene and the presence of cardiovascular risk factors, 209 patients with NIDDM and 452 subjects investigated for coronary artery disease (CAD) were studied. In the NIDDM subjects 22 (10.5%) were hete rozygous at codon 972 for a polymorphism which codes for a glycine to arginine substitution and 187 (89.5%) were homozygous for the wild typ e. Patients with the mutation had lower levels of cholesterol compared with wild type (mean, 95% confidence intervals), 5.3 (4.9-5.8) vs 6.0 (5.9-6.2) mmol/l, respectively (P = 0.002), triglyceride 1.7 (1.4-2.1 ) vs 2.2 (2.0-2.4) mmol/l (P = 0.051), factor VII:C activity 109.5 (85 .5-133.5) vs 133.5 (127-140)% (P = 0.057) and PAI-1 antigen, 16.0 (10. 5-24.3) vs 22.2 (20.0-24.6) ng/ml (P = 0.054). There were no differenc es in body mass index, indices of glycaemic control, fasting insulin o r the prevalence of hypertension. In patients with CAD, 55 (12.7%) wer e carriers of the mutation (including three homozygotes) (NIDDM vs CAD , NS), Although similar trends in cholesterol, factor VII, PAI-1 antig en and triglyceride existed between carriers of the mutation and the w ild type, none reached statistical significance. The results indicate that the IRS-1 gene is not implicated in the pathogenesis of NIDDM or CAD.