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

doi:10.1016/j.cardfail.2019.04.007

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

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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)
Pages (from-to)	553-560
Number of pages	8
Journal	Journal of Cardiac Failure
Volume	25
Issue number	7
DOIs	https://doi.org/10.1016/j.cardfail.2019.04.007
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cardfail.2019.04.007

Cite this

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title = "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 < 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.",

keywords = "Heart failure, adrenergic receptor, adrenergic signaling, gene polymorphism",

author = "Johnson, {AMBER E.} and KAREN HANLEY-YANEZ and YANCY, {CLYDE W.} and TAYLOR, {ANNE L.} and FELDMAN, {ARTHUR M.} and MCNAMARA, {DENNIS M.}",

note = "Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = jul,

doi = "10.1016/j.cardfail.2019.04.007",

language = "English (US)",

volume = "25",

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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

Y1 - 2019/7

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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