Increased sympathetic nervous system activation via the β-adrenergic pathway influences the evolution of idiopathic dilated cardiomyopathy. We assessed the effects of β-adrenergic receptor variants on heart failure in idiopathic dilated cardiomyopathy. 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 β 1- adrenergic receptor; the 5′ leader cistron (LC) Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile in the β 2-adrenergic receptor; and Arg64Trp in the β 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. During a median follow-up of 33 months, 24 patients had heart failure. In a Cox univariate analysis, the β 1Gly49 and β 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 β 2-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). The Gly49 allele in the β 1-adrenergic receptor and the 5′ LC-Cys19, Arg16, and Gln27 alleles in the β 2- adrenergic receptor were associated with a lower risk of heart failure in idiopathic dilated cardiomyopathy, suggesting that the β 1- and β 2-adrenergic receptor genes are modifier genes. © 2004 by Elsevier Inc.
Association of β-adrenergic receptor polymorphisms and progression to heart failure in patients with idiopathic dilated cardiomyopathy
FORLEO, Cinzia;RESTA, Nicoletta;
2004-01-01
Abstract
Increased sympathetic nervous system activation via the β-adrenergic pathway influences the evolution of idiopathic dilated cardiomyopathy. We assessed the effects of β-adrenergic receptor variants on heart failure in idiopathic dilated cardiomyopathy. 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 β 1- adrenergic receptor; the 5′ leader cistron (LC) Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile in the β 2-adrenergic receptor; and Arg64Trp in the β 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. During a median follow-up of 33 months, 24 patients had heart failure. In a Cox univariate analysis, the β 1Gly49 and β 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 β 2-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). The Gly49 allele in the β 1-adrenergic receptor and the 5′ LC-Cys19, Arg16, and Gln27 alleles in the β 2- adrenergic receptor were associated with a lower risk of heart failure in idiopathic dilated cardiomyopathy, suggesting that the β 1- and β 2-adrenergic receptor genes are modifier genes. © 2004 by Elsevier Inc.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
