β-adrenergic receptor gene polymorphisms and β-blocker treatment outcomes in hypertension

M. A. Pacanowski, Y. Gong, R. M. Cooper-DeHoff, N. J. Schork, M. D. Shriver, T. Y. Langaee, C. J. Pepine, J. A. Johnson

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Numerous studies have demonstrated that β1- and β2-adrenergic receptor gene (ADRB1 and ADRB2) variants influence cardiovascular risk and β-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 β-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 β-blockers may be preferred in subgroups of patients defined by ADRB1 or ADRB2 polymorphisms.

Original languageEnglish (US)
Pages (from-to)715-721
Number of pages7
JournalClinical pharmacology and therapeutics
Volume84
Issue number6
DOIs
StatePublished - Dec 2008

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

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