Lack of association between 27-bp repeat polymorphism in intron 4 of the endothelial nitric oxide synthase gene and the risk of coronary artery disease

The gene encoding endothelial nitric oxide synthase (ecNOS) is a candidate gene for the mediation of initial endothelial cell damage seen in arteriosc lerosis. Although the association of ecNOS polymorphisms with hypertension has been studied extensively, there is little information regarding its ass ociation with coronary artery disease (CAD). We decided to study a 27 base- pair tandem repeat polymorphism in intron 4 of the ecNOS gene in 1043 indiv iduals (413 controls, 630 patients with CAD) who consecutively underwent co ronary angiography at our institution. The frequencies of the genotypes dra wn from 1038 individuals were 0.69, 0.28 and 0.03 in the controls and 0.73, 0.25 and 0.02 in individulas with CAD for the ecNOS4b/b, ecNOS4b/a and ecN OS4a/a genotypes, respectively (p = n.s). There was no shift of the genotyp e frequencies from the expected distribution based on the Hardy-Weinberg eq uilibrium. Neither the rare ecNOS4a allele nor the ecNOS4a/a genotype confe rred an independent risk factor for CAD in subgroups, e.g. smokers, diabeti c individuals, hypertensive individuals and individuals with a low conventi onal risk for CAD. In five individuals we identified an additional 27-bp re peat in the ecNOS gene (ecNOS4c), which occurred heterozygous with the ecNO S4b allele (ecNOS4b/c genotype). In conclusion, the ecNOS4a allele as well as the ecNOS4a/a genotype did not show a general association with CAD in th e studied European population. Even in high-risk subgroups the ecNOS4a/4a g enotype did not represent an independent risk factor for CAD. In addition, the severity of CAD was not associated with the ecNOS4a allele/ecNOS4a/a ge notype.