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 1 2019

Fingerprint

African Americans
Adrenergic Agents
Heart Failure
Cyclic GMP-Dependent Protein Kinases
Genotype
Adrenergic Receptors
Protein Subunits
GTP-Binding Proteins
Disease-Free Survival
Alleles
Quality of Life
Genes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Johnson, AMBER. E., HANLEY-YANEZ, KAREN., Yancy, C. 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
Johnson, AMBER E. ; HANLEY-YANEZ, KAREN ; Yancy, Clyde W ; TAYLOR, ANNE L. ; FELDMAN, ARTHUR M. ; MCNAMARA, DENNIS M. / Adrenergic Polymorphisms and Survival in African Americans With Heart Failure : Results From A-HeFT. In: Journal of Cardiac Failure. 2019 ; Vol. 25, No. 7. pp. 553-560.
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Johnson, AMBERE, HANLEY-YANEZ, KAREN, Yancy, CW, TAYLOR, ANNEL, FELDMAN, ARTHURM & MCNAMARA, DENNISM 2019, 'Adrenergic Polymorphisms and Survival in African Americans With Heart Failure: Results From A-HeFT', Journal of Cardiac Failure, vol. 25, no. 7, pp. 553-560. https://doi.org/10.1016/j.cardfail.2019.04.007

Adrenergic Polymorphisms and Survival in African Americans With Heart Failure : Results From A-HeFT. / Johnson, AMBER E.; HANLEY-YANEZ, KAREN; Yancy, Clyde W; TAYLOR, ANNE L.; FELDMAN, ARTHUR M.; MCNAMARA, DENNIS M.

In: Journal of Cardiac Failure, Vol. 25, No. 7, 01.07.2019, p. 553-560.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adrenergic Polymorphisms and Survival in African Americans With Heart Failure

T2 - Results From A-HeFT

AU - Johnson, AMBER E.

AU - HANLEY-YANEZ, KAREN

AU - Yancy, Clyde W

AU - TAYLOR, ANNE L.

AU - FELDMAN, ARTHUR M.

AU - MCNAMARA, DENNIS M.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - 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.

AB - 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.

KW - Heart failure

KW - adrenergic receptor

KW - adrenergic signaling

KW - gene polymorphism

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