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J Am Coll Cardiol. 2009 Jul 28;54(5):432-44. doi: 10.1016/j.jacc.2009.05.009.

Clinical and genetic modifiers of long-term survival in heart failure.

Author information

1
Center for Pharmacogenomics, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

Abstract

OBJECTIVES:

This study sought to identify genetic modifiers of beta-blocker response and long-term survival in heart failure (HF).

BACKGROUND:

Differences in beta-blocker treatment effect between Caucasians and African Americans with HF have been reported.

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 beta-blocker. Each was genotyped for beta1-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.

RESULTS:

There were 765 deaths during follow-up (median 46 months). beta-blocker treatment increased survival in Caucasians (log-rank p = 0.00038) but not African Americans (log-rank p = 0.327). Among patients not taking beta-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 beta-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).

CONCLUSIONS:

These data show that differences caused by beta-adrenergic receptor signaling pathway gene polymorphisms, rather than race, are the major factors contributing to apparent differences in the beta-blocker treatment effect between Caucasians and African Americans; proper evaluation of treatment response should account for genetic variance.

PMID:
19628119
PMCID:
PMC2749467
DOI:
10.1016/j.jacc.2009.05.009
[Indexed for MEDLINE]
Free PMC Article

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