Overview of the impact β1-adrenergic receptor gene polymorphisms have on the progression of heart failure

Abstract

Objective: to evaluate any associations that of the β1 -adrenergic receptor (β1-AR) gene polymorphism with the progression of heart failure (HF) with reduced left ventricular ejection fraction (LVEF). Materials and methods: 195 patients with of HF II-IV functional class by NYHA (130 men and 65 women, average age (61.7 ± 2.9) y.) with LV systolic dysfunction were examined (EF less than 45%). All patients in the complex therapy received β-blockers (BAB) (bisoprolol) in an individually prescribed dose. The genotyping of the Ser49Gly and Arg389Gly polymorphisms of the β1 -AR gene was carried out by polymerase chain reaction. The results of the study. Upon examination of the frequency of the genotypes of Ser49Gly and Arg389Gly polymorphisms of the β1 -AP gene and the distribution of haplotypes of these SNPs, patients with HF did not differ from the control. However, their observation over the course of one (1) year revealed a significant decrease in the patient’s heart rate and an increase in LVEF with the use of bisoprolol, only in patients with the genotypes Ser49Ser, Arg389Arg and Arg389Gly. In patients with Ser49Ser/Arg389Arg and Ser49Ser/Arg389Gly haplotypes, a reliable positive correlation between LVEF and heart rate, monitored over the course of one year was established, although patients in the subgroups with the Ser49Gly/Arg389Arg and Ser49Gly/ Arg389Gly haplotypes the changes were insignificant, while in the Ser49Ser/Gly389Gly subgroup, there was a decrease in LVEF in combination with the absence of correlation with heart rate. The highest frequency of admission to hospital, with HF decompensation, over the period of two years was observed in patients with the Ser49Ser/ Gly389Gly haplotype. According to a prospective observational study of HF course that took place over the course of five years, the highest mortality was recorded for patients with the Gly389Gly genotype. Conclusion. The most pronounced positive clinical effect of taking BAB for the period of one year was observed for patients with the HF with the Ser49Ser/Arg389Arg haplotype of the β1 -AR gene compared to that of carriers of all other haplotypes. A two-year follow-up examination found that the haplotype Ser49Ser/Gly389Gly was unfavorable for the course of HF. Carriers of the Gly389Gly genotype of β1 -AR gene polymorphism Arg389Gly have the worst five-year survival prognosis. Keywords: heart failure, β-adrenoblocker, β1 -adrenergic receptor gene, polymorphism, bisoprolol For citation: Rudyk YuS, Pyvovar SM, Bondar TM, Lozyk TV. Overview of the impact β1-adrenergic receptor gene polymorphisms have on the progression of heart failure. Journal of the National Academy of Medical Sciences of Ukraine. 2019;25 (3):296–305 (In Ukr.)