An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals with heart failure: a MERIT-HF sub-study.

Abstract

BACKGROUND:

The Glycine389 variant of the beta-1 adrenergic receptor (beta1AR) 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 beta1AR 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.

• Authors: Hazel L White, Rudolf A de Boer, Azhar Maqbool, Darren Greenwood, Dirk J van Veldhuisen, Richard Cuthbert, Stephen G Ball, Alistair S Hall, Anthony J Balmforth, MERIT-HF Study Group
• Journal: European journal of heart failure (Eur J Heart Fail) Vol. 5 Issue 4 Pg. 463-8 (Aug 2003) ISSN: 1388-9842 [Print] England
• PMID: 12921807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic beta-Antagonists
• Receptors, Adrenergic, beta-1
• Arginine
• Metoprolol
• Glycine

Topics

• Adrenergic beta-Antagonists (pharmacology)
• Aged
• Arginine (genetics)
• Blood Pressure (drug effects)
• Female
• Genotype
• Glycine (genetics)
• Heart Failure (drug therapy, genetics, mortality)
• Heart Rate (drug effects)
• Humans
• Male
• Metoprolol (pharmacology)
• Middle Aged
• Pharmacogenetics
• Polymorphism, Genetic
• Randomized Controlled Trials as Topic
• Receptors, Adrenergic, beta-1 (genetics)