© 2003 European Society of Cardiology
An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study
a Institute for Cardiovascular Research University of Leeds, Leeds, UK
b Department of Cardiology, University Hospital Groningen Groningen, The Netherlands
* Corresponding author. Tel.: +44-113-233-4807; fax: +44-113-392-5405 E-mail address: hlwhite{at}doctors.org.uk
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Abstract |
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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=0.72). This is in contrast to the highly significant benefit of Metoprolol CR/XL observed in this sub-study population, RR=0.60; CI, 0.44–0.83 (P=0.002). No effect of the polymorphism was observed on the magnitude of heart rate reduction attained by Metoprolol CR/XL.
Conclusion: In contrast to the benefits of beta-1 selective blockade, we have demonstrated that the Gly389 allele does not confer a significant mortality/morbidity benefit in heart failure patients. We have found no evidence of a pharmacogenetic effect of this biochemically functional polymorphism.
Key Words: Beta-1 adrenergic receptor • Polymorphism • Heart failure
Received November 21, 2002; Revised January 29, 2003; Accepted March 20, 2003
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