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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U2 - 10.1016/j.cardfail.2019.04.007
DO - 10.1016/j.cardfail.2019.04.007
M3 - Article
C2 - 30978507
AN - SCOPUS:85065015475
VL - 25
SP - 553
EP - 560
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
SN - 1071-9164
IS - 7
ER -