Document Detail

Alpha2C-adrenoceptor polymorphism is associated with improved event-free survival in patients with dilated cardiomyopathy.
MedLine Citation:
PMID:  16299019     Owner:  NLM     Status:  MEDLINE    
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 alpha2-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 alpha2C-adrenoceptor gene (alpha2CDel322-325) 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% beta-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 alpha2C-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: Alpha2C-adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guidelines.
Vera Regitz-Zagrosek; Berthold Hocher; Martin Bettmann; Marc Brede; Kerstin Hadamek; Carolin Gerstner; Hans Brendan Lehmkuhl; Roland Hetzer; Lutz Hein
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-11-18
Journal Detail:
Title:  European heart journal     Volume:  27     ISSN:  0195-668X     ISO Abbreviation:  Eur. Heart J.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-01     Completed Date:  2006-07-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8006263     Medline TA:  Eur Heart J     Country:  England    
Other Details:
Languages:  eng     Pagination:  454-9     Citation Subset:  IM    
DHZB, Augustenburger Platz 1, 13353 Berlin, Germany.
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MeSH Terms
Cardiac Pacing, Artificial
Cardiomyopathy, Dilated / genetics*,  mortality,  therapy
Disease-Free Survival
Gene Frequency
Heart Failure / genetics,  mortality,  therapy
Middle Aged
Polymorphism, Genetic / genetics*
Receptors, Adrenergic, alpha-2 / genetics*
Regression Analysis
Survival Analysis
Reg. No./Substance:
0/Receptors, Adrenergic, alpha-2

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