Alpha2C-adrenoceptor polymorphism is associated with improved event-free survival in patients with dilated cardiomyopathy.
OBJECTIVE
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).


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).


CONCLUSIONS
Alpha2C-adrenoceptor deletion may be a novel, strong, and independent predictor of reduced event rates in DCM patients treated according to guidelines.
Regitz-Zagrosek
Vera
V
DHZB, Augustenburger Platz 1, 13353 Berlin, Germany. vrz@dhzb.de
Hocher
Berthold
B
Bettmann
Martin
M
Brede
Marc
M
Hadamek
Kerstin
K
Gerstner
Carolin
C
Lehmkuhl
Hans Brendan
HB
Hetzer
Roland
R
Hein
Lutz
L
D000328:Adult; D000368:Aged; D002304:Cardiac Pacing, Artificial; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000235:genetics / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012044:Regression Analysis; D016019:Survival Analysis
D018341:Receptors, Adrenergic, alpha-2