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

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

Keywords

Heart failure
adrenergic receptor
adrenergic signaling
gene polymorphism

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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@article{702eead56fc24a3ca3f949a1df35b5ae,

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 = "Funding Information: Funding: This study was supported by NIH contracts MD009118 and HL69912. Publisher Copyright: {\textcopyright} 2019",

year = "2019",

month = jul,

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

language = "English (US)",

volume = "25",

pages = "553--560",

journal = "Journal of Cardiac Failure",

issn = "1071-9164",

publisher = "Churchill Livingstone",

number = "7",

}

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

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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JO - Journal of Cardiac Failure

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SN - 1071-9164

IS - 7

ER -

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

Abstract

Keywords

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