- 作者：Sharon Cresci ; Reagan J. Kelly ; Thomas P. Cappola ; Abhinav Diwan ; Daniel Dries ; Sharon L.R. Kardia ; Gerald W. Dorn II
- 关键词：heart failure ; beta-blocker ; gene polymorphism ; beta adrenergic receptor ; G-protein receptor kinase
- 刊名：Journal of the American College of Cardiology
- 出版年：2009
- 出版时间：28 July 2009
- 年：2009
- 卷：54
- 期：5
- 页码：432-444
- 全文大小：1743 K
lass=""h4"">Objectives
This study sought to identify genetic modifiers of β-blocker response and long-term survival in heart failure (HF).lass=""h4"">Background
Differences in β-blocker treatment effect between Caucasians and African Americans with HF have been reported.
lass=""h4"">Methods
This was a prospective cohort study of 2,460 patients (711 African American, 1,749 Caucasian) enrolled between 1999 and 2007; 2,039 patients (81.7 % ) were treated with a β-blocker. Each was genotyped for β1-adrenergic receptor (ADRB1) Arg389>Gly and G-protein receptor kinase 5 (GRK5) Gln41>Leu polymorphisms, which are more prevalent among African Americans than Caucasians. The primary end point was survival time from HF onset.
lass=""h4"">Results
There were 765 deaths during follow-up (median 46 months). β-blocker treatment increased survival in Caucasians (log-rank p = 0.00038) but not African Americans (log-rank p = 0.327). Among patients not taking β-blockers, ADRB1 Gly389 was associated with decreased survival in Caucasians (hazard ratio [HR]: 1.98, 95 % confidence interval [CI]: 1.1 to 3.7, p = 0.03) whereas GRK5 Leu41 was associated with improved survival in African Americans (HR: 0.325, CI: 0.133 to 0.796, p = 0.01). African Americans with ADRB1 Gly389Gly GRK5 Gln41Gln derived a similar survival benefit from β-blocker therapy (HR: 0.385, 95 % CI: 0.182 to 0.813, p = 0.012) as Caucasians with the same genotype (HR: 0.529, 95 % CI: 0.326 to 0.858, p = 0.0098).
lass=""h4"">Conclusions
These data show that differences caused by β-adrenergic receptor signaling pathway gene polymorphisms, rather than race, are the major factors contributing to apparent differences in the β-blocker treatment effect between Caucasians and African Americans; proper evaluation of treatment response should account for genetic variance.