The polymorphism of a gene β1-adrenorecepters and a long-term forecast of patients with heart failure

Abstract

Objective — to investigate of the effect of polymorphism β1-adrenorecepters (β1-AR) gene on the long-term prognosis of patients with heart failure (HF).Materials and methods. The investigation involved 195 patients with NYHA HF II—IV (130 men and 65 women, mean age was (61.7 ± 2.9)). The following inclusion criteria were applied: the signed informed consent, systolic left ventricular dysfunction. The control group consisted of 30 age- and sex-matched subjects without HF signs. The titration of the dose of β-adrenoblockers was carried out in accordance with the recommendations of the European Society of Cardiology for diagnosis and treatment of HF (2016). To determine the type of β1-AR gene polymorphism, venous blood was sampled, followed by isolation of DNA from lymphocytes by the Wolfgang method. Primers of the β1-AR gene were synthesized (two 49 and 389 alleles). With the help of polymerase chain reaction in real time mode, the types of polymorphism of the gene were determined.Results and discussion. In patients with HF, the polymorphism of the β1-AR gene of the Ser49Ser type occurs in 76.9 %, Ser49Gly in 23.1 %. Polymorphism of the β1-AR gene of the Arg389Arg type occurs in 53.3 % of patients with HF, Gly389Arg in 40 %, 7.7 % of patients are homozygous for Gly389. The haplotype of the β1-AR gene of the Ser49Ser-Arg389Arg type is found in 40.5 % of patients with HF; 28.7 % of the patients had a haplotype of Ser49Ser-Gly389Arg, 10.3 % of Ser49Gly-Gly389Arg, 12.8 % of Ser49Gly-Arg389Arg, and 7.7 % of Ser49Ser-Gly389Gly. The polymorphism β1-AR gene was correlated with morpho-functional heart parameters: the patients with Ser49Gly polymorphism had large left ventricle sizes (by 20.4 %) in comparison with homozygotes (Ser49Ser). The patients with polymorphism such as Gly389Gly have large dimensions of the left atrium (by 22.5 %) and a right ventricle (by 42.3 %) in comparison with heterozygous (Gly389Arg). The patients with HF and with the haplotype Ser49Ser-Gly389Gly have lower heart rate, large cavities of the left atrium (by 22.5 %) and right ventricle (by 42.3 %), as well as negative dynamics of the left ventricular ejection fraction (by 5.2 %) throughout the year. The most positive impact β-adrenoblockers is observed in patients with HF with the haplotype Ser49Ser-Arg389Arg β1-AR gene. According to the prospective observational study of HF flow for 5 years, despite the use of bisoprolol in patients with HF, independence from the polymorphism β1-AR gene, there is a worsening of left ventricular systolic function (reduction of ejection fraction) against a background of low heart rate. The highest mortality is observed in patients with polymorphism β1-AR Gly389Gly gene (55.6 %). The 8-year mortality of patients with HF tends to increase in the homozygous carriers of Ser49Ser β1-AR allele with respect to Ser49Gly heterozygotes (by 12.6 %, p < 0.05) and by 16.4 % (p = 0.064) with Gly389Gly genotype, compared with carriers of Arg389Gly alleles.Conclusions. The patients with polymorphism of Ser49Gly have larger left ventricle sizes in comparison with homozygotes (Ser49Ser). The patients with polymorphism such as Gly389Gly have large dimensions of the left atrium and right ventricle as compared to heterozygous (Gly389Arg). The patients with HF and with the haplotype Ser49Ser-Gly389Gly have a low heart rate, large cavities of the left atrium and right ventricle, as well as negative dynamics of the left ventricular ejection fraction throughout the year. The most positive effect of β-adrenoblockers is observed in patients with HF with a Ser49Ser-Arg389Arg haplotype β1-AR gene. For 5 years, despite the use of bisoprolol, in patients with HF, regardless of the polymorphism of the β1-AR gene, there is a deterioration in the systolic function of the left ventricle against a background of low heart rate. The highest mortality was observed in patients with polymorphism of the β1-AR Gly389Gly gene. The 8-year mortality of patients tends to increase in the homozygous carriers of Ser49Ser β1-AR allele.