The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure.
OBJECTIVE
Discordant results have been published regarding a possible association between beta-adrenoreceptor (betaAR) gene polymorphisms and survival in patients with congestive heart failure (CHF). The aim of the study was to analyze the impact of five functional betaAR gene polymorphisms in patients with stable CHF.


METHODS
We prospectively studied 444 consecutive patients with CHF related to left ventricular systolic dysfunction. The beta1ARSer49Gly, beta1ARGly389Arg, beta2AR Arg16Gly, beta2AR Gln27Glu and beta2AR Thr164Ile polymorphisms were determined. Patients underwent echocardiography, radionuclide angiography and a cardiopulmonary exercise test.


RESULTS
Mean age was 56.6+/-11.9 years old, left ventricular ejection fraction (LVEF) was 32+/-12%, and peak VO2 was 15.5+/-4.9 ml/min/kg or 63+/-18% of maximal predicted VO2. Most of the patients (95%) were receiving angiotensin converting enzyme inhibitors and 91% beta-blockers. There was no statistically significant differences between baseline characteristics among beta1AR and beta2AR genotypes. During a median follow-up period of 1232 days, there were 110 cardiac-related deaths and five urgent transplantations. Independent predictors of survival were percent (%) of maximal predicted VO2 (p<0.0001), age (p<0.0001), LVEF (p=0.004), creatinine (p=0.02) and atrial fibrillation (p=0.04). No betaAR polymorphisms were associated with survival. However, patients with the combined beta2ARGly16Gly/beta2ARGln27Gln genotype, who express receptors highly sensitive to down-regulation, had a significantly lower survival rate than patients with other genotypes but only in univariate analysis.


CONCLUSIONS
In this prospective study, we found no association between five functional betaAR polymorphisms and survival in patients with stable CHF. However, we demonstrated, only in univariate analysis, a possible association between the combined beta2ARGly16Gly/beta2ARGln27Gln genotype and survival.
de Groote
Pascal
P
Service de Cardiologie C, Hôpital Cardiologique, Centre Hospitalier Régional et Universitaire de Lille, Boul Prof J Leclercq, 59037 Lille cedex, France. pdegroote@chru-lille.fr
Lamblin
Nicolas
N
Helbecque
Nicole
N
Mouquet
Frédéric
F
Mc Fadden
Eugène
E
Hermant
Xavier
X
Amouyel
Philippe
P
Dallongeville
Jean
J
Bauters
Christophe
C
D000368:Aged; D000704:Analysis of Variance; D001483:Base Sequence; D002423:Cause of Death; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006333:Heart Failure / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D006334:Heart Function Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015996:Survival Rate
D005819:Genetic Markers; D018342:Receptors, Adrenergic, beta-1