Abstract 15921: Alpha-2C Adrenergic Receptor Genotype is Strongly Associated With Changes in the Beta1-gene Signaling Network in Nonischemic Dilated Cardiomyopathy Patients Undergoing Beta-blocker Therapy

Introduction: Polymorphisms of adrenergic receptors (AR) may affect susceptibility for heart failure with reduced ejection fraction (HFrEF) and response to beta-blockers. One such polymorphism is deletion at amino acid residues 322-325 in the α2C AR. The purpose of this study was to determine whether this α2C genotype affects change myocardial gene expression in patients with HFrEF treated with β-blockers. Hypothesis: Expression of genes in β1-AR signaling network (β1GSN) would be differentially expressed in subjects with HFrEF and α2C wildtype (wt) genotype vs. 322-25 indel carriers (del) who show ventricular reverse remodeling with β-blocker therapy. Methods: Forty-seven patients with HFrEF were randomized to β-AR blockade with metoprolol, metoprolol + doxazosin, carvedilol. LVEF response (R) was defined as an increase of ≥ 8 units at 12 months or ≥ 5 at 3 months. Gene expression was measured by Affymetrix HGU133 plus 2.0 microarray. For each polymorphism two tailed Wilcoxon tests were performed for gen...