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 betaAR gene polymorphisms on the effects of beta-blockade. The objective of the study is to analyse the association between genetic variations in the beta1 or the beta2 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 beta1ARGly389Arg, beta1ARSer49Gly, beta2ARGly16Arg, beta2ARGln27Glu and beta2ARThr164Ile 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 beta1AR or the beta2AR polymorphisms. betaAR polymorphisms did not explain the interindividual variability in the response to beta-blockers.
de Groote
Pascal
P
Service de Cardiologie C, Hôpital Cardiologique, Centre Hospitalier Universitaire de Lille, Lille, France. pdegroote@chru-lille.fr
Helbecque
Nicole
N
Lamblin
Nicolas
N
Hermant
Xavier
X
Mc Fadden
Eugène
E
Foucher-Hossein
Claude
C
Amouyel
Philippe
P
Dallongeville
Jean
J
Bauters
Christophe
C
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000483:Alleles; D000792:Angiography; D017298:Bisoprolol / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D003062:Codon; D015536:Down-Regulation; D004452:Echocardiography; D005260:Female; D005787:Gene Frequency; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011412:Propanolamines / Q000494:pharmacology; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D003062:Codon; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D000077261:Carvedilol; D017298:Bisoprolol