β-Adrenergic Receptor Gene Polymorphisms and β-Blocker Treatment Outcomes in Hypertension

被引:98
作者
Pacanowski, M. A. [1 ,2 ]
Gong, Y. [1 ,2 ]
Cooper-DeHoff, R. M. [3 ]
Schork, N. J. [4 ]
Shriver, M. D. [5 ]
Langaee, T. Y. [1 ,2 ]
Pepine, C. J. [3 ]
Johnson, J. A. [1 ,2 ,3 ]
机构
[1] Univ Florida, Coll Pharm, Dept Pharm Practice, Gainesville, FL 32610 USA
[2] Univ Florida, Coll Pharm, Ctr Pharmacogen, Gainesville, FL USA
[3] Univ Florida, Coll Med, Dept Med, Div Cardiovasc Med, Gainesville, FL USA
[4] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
[5] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/clpt.2008.139
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:715 / 721
页数:7
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