New risk factors for coronary artery disease: the endothelial nitric oxide synthase polymorphisms

Abstract number: P0392

Sofi F., Gensini F., Fatini C., Sticchi E., Attanasio M., Lenti M., Margheri M., Giglioli C., Comeglio M., Abbate R., Gensini G. F.

University of Florence, Italy

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS) encoded by the eNOS gene on chromosome 7, plays important roles in normal vascular homeostasis and its continuos generation serves to maintain basal vascular tone. It has been suggested that endothelial NO may have an important atheroprotective role beyond its effect on vessel tone and blood pressure. An alteration in the activity of the vascular NO system could contribute to the pathogenesis of atherosclerosis. In the eNOS gene various polymorphisms have been identified The T-786C, G894T and 4a/4b polymorphisms have been demonstrated to modulate the eNOS gene expression and eNOS activity. Aim of our study was to investigate the role of these polymorphisms in 368 patients with coronary artery disease referred to the Coronary Intensive Therapy Unit of the University of Florence, compared to 268 healthy controls. The eNOS polymorphisms have been analyzed by PCR–RFLP (restriction fragment length polymorphism) analysis. As far as T-786C and 4a/4b polymorphisms are considered, the genotype distribution and allele frequency were significantly different between patients and controls (T-786C: P = 0003 and P = 00009; 4a/4b: P = 002 and P = 001). The univariate analysis showed that CC and 4a/4a genotypes are associated with the risk of coronary artery disease (CC vs. TC + TT: OR = 171, P = 001; 4a/4a vs. 4a/4b + 4b/4b: OR = 426, P = 002). As far as G894T polymorphism is considered, a significant difference in allele frequency (P = 004), but not in genotype distribution was observed between patients and controls. No association between the rare 894T allele and the disease was found. Our results suggest a role of T-786C and eNOS polymorphisms as risk factors for coronary artery disease and allow a better evaluation of the contribution of NO in the pathogenesis of the disease.