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 < 0.001). By contrast, the impact of ADRB1 Arg389Arg genotype was magnified among subjects with GNB3 825 TT genotype (n = 181, 66.3% vs 85.7%, 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.
Original language | English (US) |
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Pages (from-to) | 553-560 |
Number of pages | 8 |
Journal | Journal of Cardiac Failure |
Volume | 25 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2019 |
Funding
Funding: This study was supported by NIH contracts MD009118 and HL69912.
Keywords
- Heart failure
- adrenergic receptor
- adrenergic signaling
- gene polymorphism
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine