Genetic polymorphisms of p 53 mediated apoptosis predisposing for progression of coronary artery disease after primary CABG

Introduction: Progression of coronary artery disease (CAD) after primary coronary artery bypass grafting (CABG) is frequent and may lead to recurrent symptoms. Various data indicate that apoptosis is main event occurring during development and progression of atherosclerotic plaque. Plaque vascular smooth muscle cells (VSMCs) are more sensitive than normal VSMCs to p53-mediated apoptosis. Methods: We investigated EDTA blood of 198 patients (18% female, age: 59.2±8.4 years) who had primary CABG more than 5 years ago. CAD progression was defined as clinical endpoints: reoperation (n=88; 46%), reintervention (n=58; 30%), or angina at follow up (n=89; 46%). Apoptotic gene polymorphisms (Toll like receptor 2 A753G, Fas ligand C- 844T, Fas promotor G-670A, p 53 Arg72Pro, and CD14 C-260T) were investigated and compared to healthy controls (n=200, 24% female, age: 63.4±5.4). Results: Heterocygous, homocygous and wild type expression of all 5 genetic polymorphisms did show almost identical distribution between patients with coronary artery disease and healthy controls. Looking at clinical endpoints, we found that patients with homocygous expression of p53 polymorphisms (n=3) were prone to get a reintervention after prior CABG (p=0.03), but not reoperation. There was statistical significance of FAS promotor polymorphism to suffer from recurrent symptoms, when patients had homocygous expression (n=28, p=0.04). With wild type expression of toll like receptor 2 polymorphism and wild type of FAS promotor polymorphism results showed almost statistical significance (p=0.09) for recurrent symptoms and reintervention. Conclusions: Homocygous expression of P53 and FAS promotor polymorphisms may contribute to CAD progression.