The maintenance of balance between nitric oxide (NO) and the superoxide anion is required for proper functioning of the endothelium. To investigate the relationship between genetic factors associated with endothelial function and the development of coronary artery disease (CAD), endothelial nitric oxide synthase (ecNOS) gene a/b polymorphism and NADH/NADPH oxidase p22 phox gene C242T polymorphism were examined in 305 Korean male CAD patients and 215 healthy male control subjects. The beta-fibrinogen gene H1/H2 polymorphism was also analyzed. Both ecNOS a/b and p22 phox C242T polymorphisms were found to be associated with the development of CAD in the study population (p=0.020 and 0.011, respectively). When the association was analyzed by age, statistical significance was retained only in those <51 years (p=0.021 and 0.025 for the a/b and the C242T polymorphism, respectively) and not in those >51 years of age (p=0.155 and 0.278 respectively). However, the distribution of the beta-fibrinogen H1/H2 genotypes was not found to be associated with the development of CAD in either the < or =50 (p = 0.611) or >50 groups (p = 0.188). The ecNOS gene a/b polymorphism and the NADH/NADPH oxidase p22 phox gene C242T polymorphism were found to be significantly associated with the development of CAD in Korean male patients less than 51 years old.