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Pharmacogenetic Associations of beta 1-Adrenergic Receptor Polymorphisms With Cardiovascular Outcomes in the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes)
Journal article   Open access   Peer reviewed

Pharmacogenetic Associations of beta 1-Adrenergic Receptor Polymorphisms With Cardiovascular Outcomes in the SPS3 Trial (Secondary Prevention of Small Subcortical Strokes)

Oyunbileg Magvanjav, Caitrin W. McDonough, Yan Gong, Leslie A. McClure, Robert L. Talbert, Richard B. Horenstein, Alan R. Shuldiner, Oscar R. Benavente, Braxton D. Mitchell, Julie A. Johnson, …
Stroke (1970), v 48(5), p1337
01 May 2017
DOI: https://doi.org/10.1161/STROKEAHA.116.015936
PMID: 28351962
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1161/strokeaha.116.015936View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze),  Open
url
https://doi.org/10.1161/STROKEAHA.116.015936View
Published, Version of Record (VoR) Open

Abstract

Cardiovascular System & Cardiology Clinical Neurology Life Sciences & Biomedicine Neurosciences & Neurology Peripheral Vascular Disease Science & Technology
Background and Purpose-Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and beta-blocker response outcomes. Herein we examined associations of these polymorphisms with major adverse cardiovascular events (MACE), with and without stratification by beta-blocker treatment in patients with a history of stroke. Methods-Nine hundred and twenty-six participants of the SPS3 trial's (Secondary Prevention of Small Subcortical Strokes) genetic substudy with hypertension were included. MACE included stroke, myocardial infarction, and all-cause death. Kaplan-Meier and multivariable Cox regression analyses were used. Because the primary component of MACE was ischemic stroke, we tested the association of Ser49Gly with ischemic stroke among 41 475 individuals of European and African ancestry in the NINDS (National Institute of Neurological Disorders and Stroke) SiGN (Stroke Genetics Network). Results-MACE was higher in carriers of the Gly49 allele than in those with the Ser49Ser genotype (10.5% versus 5.4%, log-rank P=0.005). Gly49 carrier status was associated with MACE (hazard ratio, 1.62; 95% confidence interval, 1.002.68) and ischemic stroke (hazard ratio, 1.81; 95% confidence interval, 1.01-3.23) in SPS3 and with small artery ischemic stroke (odds ratio, 1.14; 95% confidence interval, 1.03-1.26) in SiGN. In SPS3, beta-blocker-treated Gly49 carriers had increased MACE versus non-beta-blocker-treated individuals and noncarriers (hazard ratio, 2.03; 95% confidence interval, 1.20-3.45). No associations were observed with the Arg389Gly polymorphism. Conclusion-Among individuals with previous small artery ischemic stroke, the ADRB1 Gly49 polymorphism was associated with MACE, particularly small artery ischemic stroke, a risk that may be increased among a-blocker-treated individuals. Further research is needed to define a-blocker benefit among ischemic stroke patients by ADRB1 genotype.

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20 citations in Web of Science
24 citations in Scopus

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Clinical Neurology
Peripheral Vascular Disease
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