An evaluation of the beta-1 adrenergic receptor Arg389Gly polymorphism in individuals at risk of coronary events. A WOSCOPS substudy

Abstract

Aims: The Glycine389 variant of the beta-1 adrenergic receptor generates markedly less cAMP when stimulated in vitro than the more prevalent Arginine389 variant and may confer protection against coronary events similar to that observed with beta-blockers. The aim of this study was to ascertain whether this Glycine389 variant protects against coronary events.

Methods and results: We identified the genotype at position 389 of the beta1AR in 1554 individuals taken from men enrolled in the West of Scotland Coronary Prevention Study. Men with a coronary event (event group) were each matched for age and smoking status with two control subjects from the same cohort who had not had a coronary event (control group). We compared the distribution of genotypes in the event and control groups. Conditional logistic regression was used to calculate odds ratios for each of the genotypes. The prevalence of the three genotypes in the entire cohort was ArgArg 53.5%, ArgGly 39.6%, GlyGly 6.9%. The Arg389Gly beta-1 adrenergic receptor polymorphism was not associated with coronary events. Using the ArgArg genotype as the reference, the odds ratio for the ArgGly genotype was 1.1 (95% CI, 0.88-1.38) and for the GlyGly genotype it was 1.05 (95% CI, 0.68-1.62).

Conclusion: Our longitudinal case-control study demonstrates that the Glycine389 variant of the beta-1 adrenergic receptor does not protect against coronary events.