Genetic polymorphisms of Renin-Angiotensin-System (RAS) as predisposing factors of coronary artery disease after primary CABG

Introduction: Genetic polymorphisms of angiotensin I converting enzyme (ACE) and angiotensin II type 1 receptor (AT-1), are considered to contribute to coronary artery disease (CAD). Endothelin converting enzyme (ECE)-1 has been identified in the vascular endothelium. Endothelin 1 regulates vascular tone and blood pressure. Progression of coronary artery disease (CAD) after primary coronary artery bypass grafting (CABG) is frequent and leads to recurrent angina, myocardial infarction, and reinterventions. Methods: We investigated EDTA blood of 198 patients (18% female, age: 59.2±8.4 years) who had primary CABG at our institution more than 5 years ago. Progression of CAD was defined as need for reoperations (n=88; 46%), reinterventions (n=58; 30%), or angina at follow up (n=89; 46%). Polymorphisms of candidate genes encoding for RAS components (ACE I/D, AT-1 1166C and ECE-1 C338A) were investigated and compared to healthy controls (n=200, 24% female, age: 63.4±5.4). Results: In CAD patients, 76 had D allel expression (homocygous for deletion=wild type), 40 homocygous for insertion and 79 heterocygous expression of ACE polymorphism. In the control group, there were 56 with D allel, 41 homocygous for insertion and 103 heterocygous, respectively (p=0.02). ECE and AT-1 R polymorphisms did not reveal differences between CAD patients and healthy controls. From 88 reoperated patients 38.6% had ACE D allel, 43 had homocygous insertion and 18.2% heterocygous genotype (n.s.). Conclusions: Homocygous genotype of ACE I/D is associated with higher ACE levels and therefore may predispose CAD progression. Patients carrying this genotype should receive ACE- Inhibitors.