European Heart Journal Advance Access originally published online on November 18, 2005
European Heart Journal 2006 27(4):454-459; doi:10.1093/eurheartj/ehi659
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
2C-Adrenoceptor polymorphism is associated with improved event-free survival in patients with dilated cardiomyopathy
1DHZB, Augustenburger Platz 1, 13353 Berlin, Germany
2Center for Cardiovascular Research Charité, University-Medicine Berlin, Hessische Str 3-4, 10115 Berlin, Germany
3Division of Nephrology, Inselspital, University of Berne, CH-3008 Berne, Switzerland
4Institute of Pharmacology and Toxicology, University of Freiburg, Germany
Received 17 May 2005; revised 19 October 2005; accepted 27 October 2005; online publish-ahead-of-print 18 November 2005.
* Corresponding author. Tel: +49 30 45932230; fax: +49 30 45932409. E-mail address: vrz{at}dhzb.de
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 
2-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 2C-adrenoceptor gene (2CDel322–325) 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% ß-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 2C-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 2C-Adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guidelines.
Key Words: Adrenoceptors • Dilated cardiomyopathy • Chronic heart failure
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Gilsbach, M. Brede, N. Beetz, E. Moura, V. Muthig, C. Gerstner, F. Barreto, S. Neubauer, M. A. Vieira-Coelho, and L. Hein Heterozygous {alpha}2C-adrenoceptor-deficient mice develop heart failure after transverse aortic constriction Cardiovasc Res, September 1, 2007; 75(4): 728 - 737. [Abstract] [Full Text] [PDF]
|
|