beta 1- and beta 2-adrenergic receptor gene beta-blocker use and risk of myocardial infarction and stroke

BACKGROUND The benefits of beta-blocker therapy may depend on underlying genetic susceptibility. METHODS We investigated the interaction of common variation in beta 1 and beta 2 adrenergic receptor (AR) genes with beta-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. RESULTS We observed an interaction of beta-blocker use with beta 1-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 anti hypertensive medications, beta-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 (Cl); 1.26-5.60) but not in homozygous carriers of the common allele (OR: 0.88,95% Cl: 0.73-1.07). Another variant, rs#2429511, interacted with beta-blocker use on both MI and ischemic stroke risks. P-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24,95% Cl: 1.03-1.50) but not in homozygous carriers of common allele (OR: 0.70,95% Cl: 0.51-0.94). P-blocker use did not interact with beta 2-AR gene variation on the risks of MI and ischemic stroke. CONCLUSIONS These results, which require replication, suggest genetic variants in the beta 1-AR gene may determine whether to use beta-blockers in hypertension for the primary prevention of cardiovascular disease.