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 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. 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 β1-adrenergic receptor; the 5′ leader cistron (LC) Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile in the β2-adrenergic receptor; and Arg64Trp in the β3-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 β1Gly49 and β2 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 β2-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). Conclusion The Gly49 allele in the β1-adrenergic receptor and the 5′ LC-Cys19, Arg16, and Gln27 alleles in the β2-adrenergic receptor were associated with a lower risk of heart failure in idiopathic dilated cardiomyopathy, suggesting that the β1- and β2-adrenergic receptor genes are modifier genes. 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 β1-adrenergic receptor; the 5′ leader cistron (LC) Arg19Cys, Arg16Gly, Gln27Glu, and Thr164Ile in the β2-adrenergic receptor; and Arg64Trp in the β3-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 β1Gly49 and β2 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 β2-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 β1-adrenergic receptor and the 5′ LC-Cys19, Arg16, and Gln27 alleles in the β2-adrenergic receptor were associated with a lower risk of heart failure in idiopathic dilated cardiomyopathy, suggesting that the β1- and β2-adrenergic receptor genes are modifier genes.