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Role of β adrenergic receptor polymorphisms in heart failure: Systematic review and meta‐analysis
Author(s) -
Muthumala Amal,
Drenos Fotios,
Elliott Perry M.,
Humphries Steve E.
Publication year - 2008
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2007.11.008
Subject(s) - medicine , heart failure , meta analysis , adrenergic receptor , ejection fraction , pathogenesis , pharmacogenetics , beta (programming language) , receptor , blockade , cardiology , adrenergic , bioinformatics , genotype , gene , genetics , biology , computer science , programming language
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 β 1 AR 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.