Association between the eNOS (Glu298Asp) and the RAS genes polymorphisms and premature coronary artery disease in a Turkish population

Abstract

Background: The renin-angiotensin system (RAS) and endothelial nitric oxide (NO) affect the pathogenesis of atherosclerosis and prognosis of coronary artery disease (CAD). Previous epidemiologic data suggested that genetic factors are more likely to affect young rather than old people. Our objective was to investigate the association between the polymorphisms of eNOS (Glu298Asp) and the RAS genes and premature CAD in a Turkish population.

Methods: A total of 115 Turkish patients with premature CAD and 83 controls were included in the study. ACE I/D, AT1R A/C, AGT T/M and eNOS Glu298Asp gene polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

Results: It was found that increased premature CAD risk is associated with higher frequencies of the ACE DD [OR: 2.600 (CI 95% 1.395-4.847, p=0.002)], AGT MM [OR=2.407 (CI 95% 1.267-4.573, p=0.007)] and eNOS 894TT [OR=17.000 (CI 95% 3.952-73.125, p<0.001)] genotypes. Carriers of ACE DD+eNOS 894TT (p=0.002), AGT MM+eNOS 894TT (p=0.001), AT1R AA+eNOS 894TT and AT1R non-AA+eNOS 894TT (p=0.002) genotypes were significantly associated with the risk of premature CAD.

Conclusions: This study indicates a synergistic contribution of RAS genes (ACE I/D, AGT T/M, AT1R T/C) and eNOS Glu298Asp polymorphisms to the development of the premature CAD.