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Lemaitre, R.N. et al.

Rozenn N. Lemaitre, Susan R. Heckbert, Nona Sotoodehnia, Joshua C. Bis, Nicholas L. Smith, Kristin D. Marciante, Lucia A. Hindorff, Leslie A. Lange, Thomas S. Lumley, Kenneth M. Rice, Kerri L. Wiggins, Bruce M. Psaty,

beta1- and beta2-adrenergic receptor gene variation, 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 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. RESULTS: 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. CONCLUSIONS: 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.[1]

References

beta1- and beta2-adrenergic receptor gene variation, beta-blocker use and risk of myocardial infarction and stroke. Lemaitre, R.N., Heckbert, S.R., Sotoodehnia, N., Bis, J.C., Smith, N.L., Marciante, K.D., Hindorff, L.A., Lange, L.A., Lumley, T.S., Rice, K.M., Wiggins, K.L., Psaty, B.M. Am. J. Hypertens. (2008) [Pubmed]

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