An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study
- 作者：White ; Hazel L. ; de Boer ; Rudolf A. ; Maqbool ; Azhar ; Greenwood ; Darren ; van Veldhuisen ; Dirk J. ; et. al.
- 关键词：Beta-1 adrenergic receptor ; Polymorphism ; Heart failure
- 刊名：European Journal of Heart Failure
- 出版年：2003
- 期刊代码：90_13889842
- 类别：med
- 出版时间：August, 2003
- 卷：5
- 期：4
- 页码：463-468
- 文件大小：451 K
摘要
Background: The Glycine389 variant of the beta-1 adrenergic receptor (β1AR) generates markedly less cAMP when stimulated in vitro than the more prevalent Arginine389 variant. Aims: The aim of this MERIT-HF sub-study was to ascertain whether this Glycine389 variant favourably influences outcome in heart failure similar to that observed with beta-blockers. Methods: We identified the genotype at amino acid 389 of the β1AR in 600 patients enrolled in the MERIT-HF study (UK and Dutch participants). A risk-ratio (RR) for each genotype was calculated using the combined endpoint of all cause mortality or hospitalisation (time to first event). A pharmacogenetic effect of this polymorphism was also sought by evaluating the effect of Metoprolol CR/XL on heart rate amongst the three genotypes. Results: The prevalence of the three genotypes was ArgArg 51.3%, ArgGly 40.2%, GlyGly 8.5%. The presence of the Gly allele was not associated with a significant benefit on the combined endpoint, RR=0.94; confidence intervals (CI), 0.69–1.29 (P