Combined renin-angiotensin system gene polymorphisms and outcomes in coronary artery disease - a preliminary report.

Background: Common variants of the renin-angiotensin system (RAS) genes have been linked to a higher risk of coronary artery disease (CAD) and its complications.

Aim: To determine the prognostic significance of a combination of three common polymorphisms of RAS genes (angiotensin converting enzyme - ACE Ins/Del, angiotensin receptor type 1 - AGT1R A1166C and angiotensinogen - ATG M235T) in patients with CAD.

Methods: The study included 216 patients (mean age 58 ± 9 years, 74% male) prospectively followed for a mean 41 ± 17 months. The end-points were all-cause mortality, myocardial infarction, stroke or the need for coronary revascularisation.

Results: An end-point occurred in 41 (19%) patients. None of the polymorphisms analysed separately was associated with the end-point. Odds ratios were calculated for different combinations of analysed alleles to determine their relation to outcomes. Based on the cut-off points of odds ratios, the study group was divided into three subgroups: 55 patients without ATG 235T allele (T- subgroup); 100 patients with ATG 235T allele alone or ATG 235T allele combined with ACE Del allele or AGT1R 1166C allele (T+ or T+1 subgroup); and 61 patients with all three variants (T+2 subgroup). Multivariate analysis showed that the only independent predictor of the endpoint was an increasing number of variant genes (HR = 2.6, 95% CI 1.4-4.9, p = 0.002).

Conclusions: Co-existing angiotensinogen M235T AGT polymorphism and two other common polymorphisms of the RAS genes are related to adverse events in patients with CAD.