TY - JOUR
T1 - β-adrenergic receptor gene polymorphisms and β-blocker treatment outcomes in hypertension
AU - Pacanowski, M. A.
AU - Gong, Y.
AU - Cooper-DeHoff, R. M.
AU - Schork, N. J.
AU - Shriver, M. D.
AU - Langaee, T. Y.
AU - Pepine, C. J.
AU - Johnson, J. A.
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
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U2 - 10.1038/clpt.2008.139
DO - 10.1038/clpt.2008.139
M3 - Article
C2 - 18615004
AN - SCOPUS:56549129495
SN - 0009-9236
VL - 84
SP - 715
EP - 721
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 6
ER -