title: The recipient's heme oxygenase-1 promoter region polymorphism is associated with cardiac allograft vasculopathy.
abstract: Heme oxygenase-1 (HO-1) catalyses the degradation of heme to biliverdin, free iron, and carbon monoxide. The promoter region contains a highly polymorphic (GT)nrepeat, where shorter (GT)nrepeat sequences are linked to higher transcriptional activity, which was shown to correlate with a cytoprotective effect. Higher HO-1 levels may protect from cardiac allograft vasculopathy. Cardiac allograft recipients transplanted between 1988 and 2012 were analyzed for the HO-1 (GT)nrepeat polymorphism using PCR and DNA fragment analysis with capillary electrophoresis. A relation to cardiac allograft vasculopathy (CAV) was analyzed using Cox regression including common risk factors for CAV and the occurrence of rejection episodes as explanatory variables. A total of 344 patients were analyzed, of which 127 patients were positive for CAV (36.9%). In our multivariable Cox regression analysis, the short homozygous HO-1 (GT)ngenotype with <27 repeats (S/S) revealed a higher risk for CAV (P = 0.032). Donor age (P = 0.001) and donor weight (P = 0.005) were significant predictors for CAV. A potential risk for CAV was associated with rejection episodes (P = 0.058) and history of smoking (P = 0.06). The recipient HO-1 (GT)ngenotype may contribute to CAV development. This finding has to be evaluated in larger series including studies targeting the underlying disease mechanism.
authors.affiliation: Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Freystaetter
authors.affiliation: Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Andreas
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Perkmann
authors.affiliation: Section for Clinical Biometrics, Center for Medical Statistics Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.affiliation: Department of Cardiology, Bologna University Hospital, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Masetti
authors.affiliation: Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Alfred
authors.initials: A
authors.lastname: Kocher
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.affiliation: Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zuckermann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014652:Vascular Diseases / Q000235:genetics*; D055815:Young Adult
chemical_list: D051547:Heme Oxygenase-1
keywords: cardiac allograft vasculopathy; cardiac transplantation; heme oxygenase-1; polymorphism