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Am J Hypertens. 2008 Mar;21(3):290-6. doi: 10.1038/ajh.2007.71. Epub 2008 Jan 24.

beta1- and beta2-adrenergic receptor gene variation, beta-blocker use and risk of myocardial infarction and stroke.

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Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.



The benefits of beta-blocker therapy may depend on underlying genetic susceptibility.


We investigated the interaction of common variation in beta1 and beta2 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.


We observed an interaction of beta-blocker use with beta1-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, 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 (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 beta-blocker use on both MI and ischemic stroke risks. beta-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). beta-blocker use did not interact with beta2-AR gene variation on the risks of MI and ischemic stroke.


These results, which require replication, suggest genetic variants in the beta1-AR gene may determine whether to use beta-blockers in hypertension for the primary prevention of cardiovascular disease.

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