Adrenergic Polymorphisms and Survival in African Americans with Heart Failure: Results from A-HeFT

ABSTRACT Background Polymorphisms in adrenergic signaling affect the molecular function of adrenergic receptors and related proteins. The β1 adrenergic receptor (ADRB1) Arg389Gly, G-protein receptor kinase type 5 (GRK5) Gln41Leu, G-protein β-3 subunit (GNB3) 825 C/T, and α2c deletion affect adrenergic tone, impact heart failure outcomes and differ in prevalence by ethnicity. Their combined effect within black cohorts remains unknown. Methods and Results We analyzed subjects from the African American Heart Failure Trial (A-HeFT) by assessing event-free survival, quality of life, and gene coinheritance. Significant coinheritance effects on survival included GRK5 Leu41 among subjects co-inheriting GNB3 825 C alleles (n = 166, 90.4% vs 69.0%, P P  = .002). The lack of the α2c deletion (ie, insertion) led to a greater impact of the ARG389Arg genotype (n = 289, 76.4% vs 86.1%, P  = .007). Conclusions Polymorphisms in adrenergic signaling affects outcomes in black subjects with heart failure. Coinheritance patterns in genetic variation may help determine heart failure survival.