© 2008 European Society of Cardiology
Role of β adrenergic receptor polymorphisms in heart failure: Systematic review and meta-analysis
a Centre for Cardiovascular Genetics, Rayne Institute, Royal Free and University College Medical School London WC1E 6JF, UK
b Inherited Cardiovascular Diseases Unit, Heart Hospital, Royal Free and University College Medical School London, UK
* Corresponding author. British Heart Foundation Laboratories, Royal Free & University College Medical School, Rayne Building, 5 University Street, London WC1E 6JF, UK. Tel.: +44 20 7679 6964; fax: +44 20 7679 6212. E-mail address: amuthumala{at}aol.com
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Abstract |
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Heart Failure (HF) is a common disorder associated with substantial morbidity and mortality. β adrenergic receptors (βAR) are the primary pathway through which cardiac function is influenced. Chronic β1AR activation is implicated in the pathogenesis of HF and βAR blockade improves survival in left ventricular systolic dysfunction. Common functional polymorphisms in β adrenergic receptor genes (ADRB) have been associated with HF phenotypes, and with pharmacogenetic interaction with β adrenergic receptor blockers (β blockers). However, these associations have not been consistently replicated. The evidence for ADRB variant involvement in pathogenesis, progression and response to β blockers in HF is reviewed. In addition, a meta-analysis of three studies analysing the effect of ADRB1 Arg389Gly polymorphism on left ventricular remodelling with the use of β blockers, demonstrating a 5% improvement in left ventricular ejection fraction in Arg389 homozygotes, is presented. There is now accumulating molecular evidence for a different functional response to β blockers associated with this polymorphism. In the future, confirmed genotypic associations may enable patients to be identified who are either at greater risk of developing HF, whose HF may rapidly progress, or who are unlikely to benefit from β blockers, and such patients may benefit from targeted aggressive therapy.
Key Words: β adrenergic receptor • Gene • Polymorphism • Heart failure
Received June 14, 2007; Revised September 18, 2007; Accepted November 19, 2007
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