1- and 2-Adrenergic Receptor Gene Variation, -Blocker Use and Risk of Myocardial Infarction and Stroke

Abstract

The benefits of β-blocker therapy may depend on underlying genetic susceptibility. We investigated the interaction of common variation in β1 and β2 adrenergic receptor (AR) genes with β-blocker use on the risks of myocardial infarction (MI) and ischemic stroke in a case–control study. Participants were treated pharmacologically for hypertension, aged 30–79 years, with incident MI (n = 659) or ischemic stroke (n = 279) between 1995 and 2004, and 2,249 matched controls. We observed an interaction of β-blocker use with β1-AR gene variation on MI risk (P value, 6 degrees of freedom: 0.01) and ischemic stroke risk (P value, 6 degrees of freedom: 0.04). Compared with use of other antihypertensive medications, β-blocker use was associated with higher MI risk in carriers of one or two copies of rs#17875422 (Odds ratio (OR): 2.66, 95% confidence interval (CI); 1.26–5.60) but not in homozygous carriers of the common allele (OR: 0.88, 95% CI: 0.73–1.07). Another variant, rs#2429511, interacted with β-blocker use on both MI and ischemic stroke risks. β-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24, 95% CI: 1.03–1.50) but not in homozygous carriers of common allele (OR: 0.70, 95% CI: 0.51–0.94). β-blocker use did not interact with β2-AR gene variation on the risks of MI and ischemic stroke. These results, which require replication, suggest genetic variants in the β1-AR gene may determine whether to use β-blockers in hypertension for the primary prevention of cardiovascular disease.