Renin-angiotensin system gene polymorphisms and premature coronary heart disease.

Experimental and clinical studies demonstrated that the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and prognosis of coronary heart disease (CHD). The aim of this study was to investigate the genotype distribution and the allele frequencies of three RAS genes polymorphisms and their effects on premature CHD in a Turkish population. One-hundred and fifteen Turkish patients with premature CHD and 128 controls were included into the study. Angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor and angiotensinogen (AGT) gene polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The patients group showed an increased frequency of the ACE D allele compared with controls (65% vs. 35%, p = 0.0001). There was a significant association between the DD genotype and premature CHD (ACE DD vs. ID and II; odds ratio [OR] = 2.82 [CI 95% 1.33 2.91, p = 0.002]). Also, we observed increased premature CHD risk associated with higher frequencies of the AGT MM genotype in patients when compared with controls (AGT MM vs. TT and MT, OR = 1.92 [CI 95% 1.11-3.33, p = 0.018]). We found a significant association between AT1-receptor AA genotype and decreased risk of premature CHD (AT1R AA vs. AC and CC, OR = 0.57[CI 95% 0.34-0.95, p = 0.03]). We demonstrated that increased premature CHD risk is associated with higher frequencies of the ACE DD and AGT MM genotypes. These findings indicate a synergistic contribution of ACE DD and AGT MM polymorphisms to the development of premature CHD. Also, our results suggest that family history, smoking, diabetes, hypertension, obesity and ACE DD genotype were independent risk factors for premature CHD.