Abstract 384: Association between Renin Angiotensin System Gene Polymorphisms and Severity of Coronary Artery Disease and Restenosis after Coronary Stenting

Abstract

Background and Objective: Coronary artery disease (CAD) represents the most important cause of sudden cardiac death. Percutaneous coronary intervention (PCI) is an effective technique for coronary revascularization but a considerable number of patients develop restenosis after stenting. Renin angiotensin system (RAS) plays an important role in restenosis by promoting neo-intimal hyperplasia. This study evaluateed the polymorphisms of the genes encoding key RAS components including angiotensinogen (AGT), angiotensin converting enzyme (ACE) and angiotensin type 1a (AT1a) receptor in relation to severity of coronary artery disease and in-stent restenosis after coronary stenting. Methods and Results: Five hundred and twenty six patients who underwent angiography due to suspected CAD were prospectively recruited to this study. Five single nucleotide polymorphisms (M235T, G217A, G152A, G-6A, A-20C) of AGT gene, ACE insertion/deletion (I/D) and AT1a A1166C polymorphisms were genotyped from genomic DNA with direct sequencing. Severity of coronary atherosclerosis was assessed by angiographic Gensini score. A subsequent coronary angiography was performed 6-9 months later for suspected restenosis for patients (N=273) who underwent coronary stent implantation. In-stent restenosis was evaluated by means of quantitative angiography. Forty-five patients (16.5%) revealed in-stent restenosis. Haplotypes were constructed after linkage disequilibrium analysis. In a multivariate analysis of angiographic restenosis, there was no significant association of the polymorphisms of AGT(M235T, G217A, G152A, G-6A, A-20C, ACE I/D, and AT1a A1166C with the occurrence of in-stent restenosis (P>0.05). However, in the CAD group, frequency of ACE D allele was significantly higher in patients with angiographically defined multi-vessel disease compared to patients with single vessel CAD ( p = 0.013). Additionally, a significant association was found between the frequency of D allele and severity of CAD assessed by the Gensini score (P=0.028). Conclusion: Genetic polymorphisms of RAS are not associated with in-stent restenosis after coronary stenting. However, the presence of the ACE I/D polymorphism is potentially associated with the severity of CAD.