心血管药理学：开放获取

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Pharmacogenetics of β₁-Adrenergic Receptor Blockers in Heart Failure Therapy: A Systematic Review

Takele Beyene Tufa, Zelalem Petros and Lidiya Fikirte Melke

Background: β1-adrenergic receptor blockers are an important drugs recommended as first-line treatment of Heart Failure (HF) as they improve survival in left ventricular systolic dysfunction due to chronic β1-Adrenergic Receptor (β1-AR) activation. However, responses to these drugs are variable among patients due to genetic polymorphism in β1-AR gene. We conducted a systematic review to summarize all published case-control and prospective studies on pharmacogenetics of β1-adrenergic receptor blockers (β1-ARBs) used for the management of HF.

Methods and findings: We performed a systematic search of the literature using Medline (source PubMed, January 1, 1980 to November 30, 2011) with restrictions for English language and polymerase chain reaction assay method of genotyping the receptor polymorphism. Both experimental and observational studies investigating the pharmacogenetics effect of β1-adrenergic receptor blockers in heart failure were included. The main outcome measure was improvement of HF symptoms which is reflected in a decrease in mortality, hospitalisation and the rate of major clinical events. Of the 30 included studies, 17 articles reporting on effect of genetic polymorphisms of β1-AR on heart failure, 11 articles reporting on pharmacogenetics of β1-ARBs in HF, and 2 articles reporting on both β1-AR gene polymorphisms and pharmacogenetics of β1-ARBs, were included into the results.

Conclusions: The findings of the current study have shown that β1-AR polymorphisms have an effect on survival and improvement in left ventricular ejection fraction in HF patients who were Arg389 homozygotes carriers treated with metoprolol and bucindolol. Therefore, the Arg389 of β1-AR variation alters the β1-ARBs therapeutic response, and might be used to individualize treatment of HF.