Adrenergic Polymorphisms and Survival in African Americans With Heart Failure: Results From A-HeFT

AMBER E. Johnson*, KAREN HANLEY-YANEZ, CLYDE W. YANCY, ANNE L. TAYLOR, ARTHUR M. FELDMAN, DENNIS M. MCNAMARA

*Corresponding author for this work

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalJournal of Cardiac Failure
Volume25
Issue number7
DOIs
StatePublished - Jul 2019

Keywords

  • Heart failure
  • adrenergic receptor
  • adrenergic signaling
  • gene polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Johnson, AMBER. E., HANLEY-YANEZ, KAREN., YANCY, CLYDE. W., TAYLOR, ANNE. L., FELDMAN, ARTHUR. M., & MCNAMARA, DENNIS. M. (2019). Adrenergic Polymorphisms and Survival in African Americans With Heart Failure: Results From A-HeFT. Journal of Cardiac Failure, 25(7), 553-560. https://doi.org/10.1016/j.cardfail.2019.04.007