Angiotensin-Converting Enzyme and Endothelial Constitutive Nitric Oxide Synthase Polymorphisms in Turkish Renal Transplant Population and Possible Influence on Renal Artery Atherosclerosis and Graft Survival

Abstract

Background Renal transplant recipients are prone to accelerated atherosclerosis secondary to immunsuppressants, which may decrease graft survival. We sought to analyze the effects on renal graft survival of atherosclerotic degeneration in the renal artery and the influence of angiotensin-converting enzyme (ACE) endothelial constitutive nitric oxide synthase (ecNOS) gene polymorphisms. Methods and patients Thirty three renal transplant recipients (25 men) of mean age 28.4 ± 9.6 years, received organs from 11 living related donors and were followed for at least 36 months. Genotyping was performed for the insertion/deletion ACE (I/D), angiotensin (AGT) (M→T, 235), angiotensine 1 receptor (A→C, 1166), angiotensin 2-receptor (A→G, 1223), and ecNOS (b→a, intron4) gene polymorphisms. Renal artery biopsies were performed during transplantation surgery to analyze the presence of atherosclerosis. Results Pathological examination indicated that 18 donor specimens and nine recipient specimens had atherosclerotic degeneration. Survival analysis (36 months) indicated that graft survival rates of recipients who had atherosclerosis in the renal artery and who received an organ from donors with an atherosclerotic renal artery were shorter than in their counterparts ( P = .02, P = .04, respectively). Comparison of genetic variations of recipients revealed that CC/TC variation of AGT was higher in patients with atherosclerosis (81% vs 53%, P = .03). There was no significant difference between groups in means of other gene polymorphisms. Conclusion Renin-angiotensin system gene polymorphism analysis of patients in renal transplantation waiting list may provide information about allograft survival and posttransplant atherosclerotic degeneration at graft vasculature of young transplant recipients.