Association Between β1-adrenergic Receptor Polymorphisms And The Response To Medication In Patients With Chronic Heart Failure

Objective:To investigatethe relationship between Ser49Gly and Arg389Gly polymorphisms in β1-adrenergic receptor (ADRB1) gene and the response to medication in patients with chronicheart failure (CHF).Methods:Two hundred and sixty consecutive in patients with CHF(LVEF<40%) were enrolled from October 2013 to April 2015.Genomic DNA was extracted from peripheral blood leukocytes and the genotypes of Ser49Gly and Arg389Gly polymorphisms were identified in all individuals by Taqman probe. All patients received standard medication to treat heart failure. During one year follow up, differences of echocardiographic parameters and major adverse cardiac events (cardiac death, heart transplantation, malignant arrhythmia, re-hospitalization for heart failure) were analyzed.Results:For Ser49Gly polymorphisms, genotype frequencies of AA, AG, GG were 78.5%,19.0%,2.5%, conforming to Hardy Weinberg law(χ2=1.537, P=0.215). There were no differences between the two groups of AA and AG/GG of baseline clinical features and echocardiographic parameters (P>0.05). Echocardiographic parameters such as left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) at 3 months,6 months and 12 months and incidence of major adverse cardiac events for one year were similar between the two groups(P>0.05).For Arg389Gly polymorphisms, genotype frequencies of CC, CG, GG were48.5%,42.3%,9.2%,conforming to Hardy Weinberg law(χ2=0.14, P=0.708). There were no significant differences in baseline clinical characteristics, left ventricular diameter and LVEF between the three genotypes (P>0.05). Drug usage rate and dosage within one year (Metoprolol, ACEI/ARB, Spironolactone) was similar between the three groups but increase amplitude of LVEF after one year follow-up of GG group was significantly higher than that of CC group (11.7% vs 1.3%, P<0.05),and the decrease amplitude of LVDd was also the case (7.1mm vs 0.6mm, P<0.05). The increase amplitude of LVEF and the decrease amplitude of LVDd of CG group were between GG group and CC group. The incidence of major adverse cardiac events in the three groups of CC, CG and GG were 22.2%,10.0% and 8.3%, respectively, with statistical difference (P=0.021). The rate of CG group was significantly lower than CC group (P=0.009), and GG group had showed the tendency to be lower when compared with CC group (P=0.094).The rate of G carries group was 9.7%, and it was significantly lower than CC homozygous (P=0.006).Conclusions:The study suggested that there was no relationship between Ser49Gly polymorphisms of the ADRB1 gene and the therapeutic effect and prognosis in patients with heart failure under the same dosage of drugs. However, the improvement of cardiac function and prognosis in patients carrying the Gly389 allele were significantly better than those of Arg389Arg homozygous, suggesting that patients with chronic heart failure might require individual drug therapy according to gene polymorphism.