Association of beta-adrenergic receptor polymorphisms and progression to heart failure in patients with idiopathic dilated cardiomyopathy.
OBJECTIVE
Increased sympathetic nervous system activation via the beta-adrenergic pathway influences the evolution of idiopathic dilated cardiomyopathy. We assessed the effects of beta-adrenergic receptor variants on heart failure in idiopathic dilated cardiomyopathy.


METHODS
We prospectively analyzed 171 consecutive patients (mean [+/- SD] age, 49 +/- 14 years; 129 men) with idiopathic dilated cardiomyopathy who were receiving conventional treatment. All were characterized by polymerase chain reaction-restriction fragment length polymorphism analysis for Ser49Gly and Arg389Gly in the beta1-adrenergic receptor; the 5' leader cistron (LC) Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile in the beta2-adrenergic receptor; and Arg64Trp in the beta3-adrenergic receptor. The endpoint was heart failure, defined as a worsening of clinical condition leading to hospitalization for heart failure, cardiac transplantation, or death from heart failure.


RESULTS
During a median follow-up of 33 months, 24 patients had heart failure. In a Cox univariate analysis, the beta1Gly49 and beta2 5'LC-Cys19, Arg16, and Gln27 alleles were associated with a lower risk of heart failure. In a multivariate analysis that considered age, functional class, left ventricular ejection fraction, and beta-blocker use, three beta2-adrenergic receptor alleles were associated with lower risk: 5'LC-Cys19 (hazard ratio [HR]: 0.15; 95% confidence interval [CI]: 0.05 to 0.42), Arg16 (HR: 0.12; 95% CI: 0.04 to 0.35), and Gln27 (HR: 0.15; 95% CI: 0.05 to 0.42).


CONCLUSIONS
The Gly49 allele in the beta1-adrenergic receptor and the 5' LC-Cys19, Arg16, and Gln27 alleles in the beta2-adrenergic receptor were associated with a lower risk of heart failure in idiopathic dilated cardiomyopathy, suggesting that the beta1- and beta2-adrenergic receptor genes are modifier genes.
Forleo
Cinzia
C
Institute of Cardiology, University of Bari, Bari, Italy.
Resta
Nicoletta
N
Sorrentino
Sandro
S
Guida
Pietro
P
Manghisi
Andrea
A
De Luca
Viviana
V
Romito
Roberta
R
Iacoviello
Massimo
M
De Tommasi
Elisabetta
E
Troisi
Federica
F
Rizzon
Brian
B
Guanti
Ginevra
G
Rizzon
Paolo
P
Pitzalis
Maria Vittoria
MV
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000704:Analysis of Variance; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics; D002423:Cause of Death; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006333:Heart Failure / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D016027:Heart Transplantation; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011943:Receptors, Adrenergic, beta / Q000235:genetics*; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics; D013564:Sympathetic Nervous System; D016277:Ventricular Function, Left
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta