Association of β-adrenergic receptor polymorphisms and progression to heart failure in patients with idiopathic dilated cardiomyopathy

PURPOSE. Increased sympathetic nervous system activation via the P-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 [+/- SDI 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 beta(1)-adrenergic receptor; the 5' leader cistron (LC) Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile in the beta(2)-adrenergic receptor; and Arg64Trp in the beta(3)-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 beta(1) Gly49 and beta(2) 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 beta(2)-adrenergic receptor alleles were associated with lower risk: 5'LC-Cys19 (hazard ratio [HR]: 0.15; 95% confidence interval [Cl]: 0.05 to 0.42), Arg16 (HR: 0.12; 95% Cl: 0.04 to 0.35), and Gln27 (HR: 0.15; 95% Cl: 0.05 to 0.42). CONCLUSION. The Gly49 allele in the beta(1)-adrenergic receptor and the 5' LC-Cys19, Arg16, and Gln27 alleles in the beta(2)-adrenergic receptor were associated with a lower risk of heart failure in idiopathic dilated cardiomyopathy, suggesting that the beta(1)- and beta(2)-adrenergic receptor genes are modifier genes.