Coronary artery disease (CAD) is a multifactorial disease which appears to be due to a number of genetic and environmental factors. The aims of our study were to investigate gene polymorphism of factors modulating endothelial function (ACE, e-NOS), thrombosis (t-PA, PAI-1, GP IIIa) and lipid metabolism (apoE) in patients with CAD, and to identify those genetic risk factors that might be related to premature CAD presentation. One hundred patients with first clinical manifestation of CAD (<50 years, n=52; greater than or equal to50 years, n=48) and 80 control subjects underwent the ACE I/D, c-NOS G/T, t-PA VD, PAI-1 4G4G, GP IIIa P1(A1/A2) and apoE epsilon2/epsilon3/epsilon4 genotyping. The ACE DD and e-NOS TT genotypes occurred significantly more frequently in CAD patients than in controls (37% vs. 21%, p <0.05) and (20% vs. 9%, p <0.05). There was no significant difference in the distribution of t-PA, PAI-1, GPIIIa and apoE polymorphisms between the two groups. By multivariate regression analysis, the ACE DD genotype conferred a 3-fold increased risk of premature CAD (95% CI 1.1"7.9, p <0.05).