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Clin Pharmacol Ther. 2008 Dec;84(6):715-21. doi: 10.1038/clpt.2008.139. Epub 2008 Jul 9.

beta-adrenergic receptor gene polymorphisms and beta-blocker treatment outcomes in hypertension.

Author information

1
Department of Pharmacy Practice and Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida, USA.

Abstract

Numerous studies have demonstrated that beta(1)- and beta(2)-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and beta-blocker responses in hypertension and heart failure. We evaluated the relationship between ADRB1 and ADRB2 haplotypes, cardiovascular risk (death, nonfatal myocardial infarction (MI), and nonfatal stroke), and atenolol-based vs. verapamil sustained-release (SR)-based antihypertensive therapy in 5,895 coronary artery disease (CAD) patients. After an average of 2.8 years, death rates were higher in patients carrying the ADRB1 Ser49-Arg389 haplotype (hazard ratio (HR) 3.66, 95% confidence interval (95% CI) 1.68-7.99). This mortality risk was significant in patients randomly assigned to verapamil SR (HR 8.58, 95% CI 2.06-35.8) but not atenolol (HR 2.31, 95% CI 0.82-6.55), suggesting a protective role for the beta-blocker. ADRB2 haplotype associations were divergent within the treatment groups but did not remain significant after adjustment for multiple comparisons. ADRB1 haplotype variation is associated with mortality risk, and beta-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2 polymorphisms.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00133692.

PMID:
18615004
PMCID:
PMC2675574
DOI:
10.1038/clpt.2008.139
[Indexed for MEDLINE]
Free PMC Article

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