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α2C-Adrenoceptor polymorphism is associated with improved event-free survival in patients with dilated cardiomyopathy

Regitz-Zagrosek, Vera ; Hocher, Berthold ; Bettmann, Martin ; Brede, Marc ; Hadamek, Kerstin ; Gerstner, Carolin ; Lehmkuhl, Hans Brendan ; Hetzer, Roland ; Hein, Lutz

In: European Heart Journal, 2006, vol. 27, no. 4, p. 454-459

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    Titre
    • α2C-Adrenoceptor polymorphism is associated with improved event-free survival in patients with dilated cardiomyopathy
    Auteur
    • Regitz-Zagrosek, Vera. DHZB, Augustenburger Platz 1, 13353 Berlin, Germany
    • Hocher, Berthold. Center for Cardiovascular Research Charité, University-Medicine Berlin, Hessische Str 3-4, 10115 Berlin, Germany
    • Bettmann, Martin. DHZB, Augustenburger Platz 1, 13353 Berlin, Germany
    • Brede, Marc. Institute of Pharmacology and Toxicology, University of Freiburg, Germany
    • Hadamek, Kerstin. Institute of Pharmacology and Toxicology, University of Freiburg, Germany
    • Gerstner, Carolin. Institute of Pharmacology and Toxicology, University of Freiburg, Germany
    • Lehmkuhl, Hans Brendan. DHZB, Augustenburger Platz 1, 13353 Berlin, Germany
    • Hetzer, Roland. DHZB, Augustenburger Platz 1, 13353 Berlin, Germany
    • Hein, Lutz. Institute of Pharmacology and Toxicology, University of Freiburg, Germany
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • European Heart Journal, 2006, vol. 27, no. 4, p. 454-459. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:300005
    Summary
    Aims The sympathetic nervous system plays a central role in cardiac growth but its overstimulation is associated with increased mortality in patients with chronic heart failure. Pre-synaptic α2-adrenoceptors are essential feedback regulators to control the release of norepinephrine from sympathetic nerves. In this study we tested whether a deletion polymorphism in the human α2C-adrenoceptor gene (α2CDel322-325) affects progression of heart failure in patients with dilated cardiomyopathy (DCM). Methods and results We genotyped and phenotyped 345 patients presenting with DCM in the heart transplant unit of the German Heart Institute, starting in 1994. Patients were treated according to guidelines (99% ACEI, 76% β-blockers) and were followed until December 2002 or until a first event [death, heart transplantation, or implantation of a left ventricular assist device (LVAD) for a life-threatening condition] occurred. Mean follow-up time was 249 weeks (4.9 years) in event-free patients and 104 weeks (2 years) in patients with events. During follow-up, 51% of the patients exhibited an event: death (18%), implantation of LVAD as bridging for transplantation (7%), or heart transplantation (25%). By Kaplan-Meier analysis, DCM patients with the deletion variant Del322-325 in the α2C-adrenoceptor showed significantly decreased event rates (P=0.0043). Cox regression analysis revealed that the presence of the deletion was associated with reduced death rate (relative risk: 0.129, 95% CI: 0.18-0.9441, P=0.044) and event rates (relative risk: 0.167, 95% CI: 0.041-0.685, P=0.012). Conclusion α2C-Adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guidelines