ACE-gene polymorphism is associated with the development of allograft vascular disease in heart transplant recipients

Background: Cardiac allograft vascular disease is (CAVD) the most important cause of death following heart transplantation (HTX). Although in the past , researchers focused predominantly on mechanisms of endothelial injury, th e possible role of recipient-related and genetically determined factors has not been studied in detail. Methods: Stimulated by recent observations in native coronary artery diseas e, we analyzed the potential impact of angiostensin-converting enzyme (ACE) polymorphism (insertion/deletion [I/D], intron 16) on development and prog ression of CAVD. We characterized genotype in 146 patients 1 to 12 years af ter HTX (121 men; mean age, 46.2 +/- 11.3 years; observation period, 6.1 +/ - 3.8 years) and correlated genotype to the onset and progression of CAVD, defined as luminal obstruction > 50%. Results: We found allelic frequencies to be 28.8% (n = 42) for ACE-DD, 49.3 % (n = 72) for ACE-DI, and 21.9% (n = 32) for ACE-II. Differences in actuar ial freedom from vasculopathy were significant 6 years after transplantatio n, with 84.6% for ACE-II compared with 54.4% for ACE-DD. We observed interm ediate results for ACE-DI genotype (77.3%, p = 0.015). Conclusions: In this large cohort study; we demonstrated a close relationsh ip between the recipient-related ACE-D genotype and development of advanced CAVD. These observations suggest that gene-environment interactions might be clinically important in coronary vasculopathy after HTX.