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, the possible role of recipient-related and genetically determined factors has not been studied in detail.


METHODS
Stimulated by recent observations in native coronary artery disease, we analyzed the potential impact of angiotensin-converting enzyme (ACE) polymorphism (insertion/deletion [I/D], intron 16) on development and progression of CAVD. We characterized genotype in 146 patients 1 to 12 years after 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 actuarial freedom from vasculopathy were significant 6 years after transplantation, with 84.6% for ACE-II compared with 54.4% for ACE-DD. We observed intermediate results for ACE-DI genotype (77.3%, p = 0.015).


CONCLUSIONS
In this large cohort study, we demonstrated a close relationship 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.
Pethig
K
K
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany.
Heublein
B
B
Hoffmann
A
A
Borlak
J
J
Wahlers
T
T
Haverich
A
A
D000206:Actuarial Analysis; D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003327:Coronary Disease / Q000209:etiology* / Q000235:genetics; D018450:Disease Progression; D004777:Environment; D005260:Female; D005500:Follow-Up Studies; D017353:Gene Deletion; D005787:Gene Frequency; D005838:Genotype; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007438:Introns / Q000235:genetics; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D016019:Survival Analysis; D014184:Transplantation, Homologous
D007703:Peptidyl-Dipeptidase A