Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure

Previous studies have clearly demonstrated the beneficial effect of beta-blockers in patients with stable congestive heart failure (CHF). beta-blockers improve left ventricular ejection fraction (LVEF) and reduce cardiac mortality. However, there is an interindividual variability in the response to these agents. Two studies have suggested a possible impact of some functional beta AR gene polymorphisms on the effects of beta-blockade. The objective of the study is to analyse the association between genetic variations in the beta(1) or the beta(2) adrenoreceptor (AR) gene and the effects of beta-blockade in patients with stable CHF. We studied 199 consecutive patients with stable CHF not treated with beta-blockers. Before introduction of beta-blockers and 3 months after the maximal tolerated dose was reached, patients underwent an echocardiography and a radionuclide angiography, The beta(1)ARGly(389)Arg, beta(1)ARSer(49)Gly, beta(2)ARGly(16)Arg, beta(2)ARGln(27)Glu and beta(2)ARThr(164)Ile polymorphisms were determined: beta-blockade resulted in a significant decrease in heart rate, a significant increase in LVEF (from 30 +/- 10% to 40 +/- 13%, P < 0.0001). There was no association between the five polymorphisms and heart rate or LVEF, either before or after beta-blockade. Heart rate and LVEF responses to beta-blockade were not associated with the beta(1)AR or the beta(2)AR polymorphisms. beta AR polymorphisms did not explain the interindividual variability in the response to beta-blockers. Pharmacogenetics and Genomics 15:137142 (c) 2005 Lippincott Williams & Wilkins.