The recipient's heme oxygenase-1 promoter region polymorphism is associated with cardiac allograft vasculopathy
Kathrin Freystaetter
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorCorresponding Author
Martin Andreas
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Correspondence
Martin Andreas, Department of Cardiac Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Tel.: +43 1 40400 69660;
fax: +43 1 40400 69680;
e-mail: [email protected]
Search for more papers by this authorMartin Bilban
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorThomas Perkmann
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAlexandra Kaider
Section for Clinical Biometrics, Center for Medical Statistics Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorMarco Masetti
Department of Cardiology, Bologna University Hospital, Bologna, Italy
Search for more papers by this authorAlfred Kocher
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorMichael Wolzt
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAndreas Zuckermann
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorKathrin Freystaetter
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorCorresponding Author
Martin Andreas
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Correspondence
Martin Andreas, Department of Cardiac Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Tel.: +43 1 40400 69660;
fax: +43 1 40400 69680;
e-mail: [email protected]
Search for more papers by this authorMartin Bilban
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorThomas Perkmann
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAlexandra Kaider
Section for Clinical Biometrics, Center for Medical Statistics Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorMarco Masetti
Department of Cardiology, Bologna University Hospital, Bologna, Italy
Search for more papers by this authorAlfred Kocher
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorMichael Wolzt
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAndreas Zuckermann
Division of Cardiac Surgery, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorSummary
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)n repeat, where shorter (GT)n repeat 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)n repeat 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)n genotype 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)n genotype may contribute to CAV development. This finding has to be evaluated in larger series including studies targeting the underlying disease mechanism.
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