Association of β1- and β2-adrenergic receptor gene polymorphisms with the risk of heart failure in patients with type 2 diabetes mellitus
Authors: Kulaiets N.M. 
Published: August 2024

Background. Heart failure (HF) is the most common cause of hospitalization and mortality in patients with cardiovascular diseases. It is known that concomitant diseases and the dynamics of some biomarkers, hormones and genetic factors are associated with the course of HF and its progression. Gene polymorphisms of β1- and β2-adrenergic receptors (β1- and β2-AR) probably play an important role in the occurrence, progression of HF and the formation of response to therapy with β-adrenergic blockers. Conducting a comprehensive analysis can add arguments in favor of a cause-and-effect relationship between polymorphisms and disease phenotypes. This encourages new research in this direction. The purpose was to study the correlation between β1- and β2-adrenergic receptor gene polymorphisms and the risk of developing heart failure. Materials and methods. Two hundred and one patients with HF on the background of post-infarction cardiosclerosis were included. Control group consisted of 43 healthy persons of comparable age and sex. Genotyping was carried out for 3 polymorphisms (Gly389Arg of the β1-AR gene, Ser49Gly of the β1-AR gene, Gln27Glu of the β2-AR gene) using the polymerase chain reaction. Echocardiography was performed. Statistical analysis was done using SPSS and SNPStats programs. Results. The A allele (A/G-A/A) of the Ser49Gly polymorphism of the β1-AR gene is associated with a reduced risk of heart failure (odds ratio (OR) = 0.45 (0.23–0.91), p = 0.029, dominant model of inheritance). Data on a decreased risk of HF in the presence of the A allele of the Ser49Gly polymorphism of the β1-AR gene are also confirmed in codominant (OR = 0.43 (0.22–0.87), p = 0.048), overdominant (OR = 0.43 (0.21–0.86), p = 0.02) and log-additive (OR = 0.51 (0.27–0.99), p = 0.051) inheritance models. During a comparative analysis of the distribution of the Ser49Gly (c.145A>G) polymorphism alleles of the β1-AR gene, a tendency towards a decrease in the frequency of the A allele in patients with HF was revealed compared to the control group (11.9 against 19.7 %, respectively; χ2 = 3.759; p = 0.053). Among patients with HF, a heterozygous genotype (G/A) occurred in 21.9 % of cases against 39.5 % in the control group (χ2 = 6.163; p = 0.046). The A allele (A/G-A/A) of the Ser49Gly polymorphism of the β1-AR gene is associated with a decreased risk of reduced left ventricular ejection fraction ≤ 40 % (OR = 0.43 (0.19–0.95), p = 0.048 in the dominant model, and OR = 0.42 (0.19–0.93), p = 0.033 in the overdominant model of inheritance). The risk of a decrease in left ventricular ejection fraction among patients with HF is lower among carriers of the G allele of the Gln27Glu polymorphic locus of the β2-AR gene (OR = 0.52 (0.30–0.92), p = 0.025). Conclusions. The risk of developing heart failure and its phenotype are associated with genetic differences in β-adrenergic receptors. The A allele of the Ser49Gly polymorphism of the β1-adrenergic receptor gene is associated with a reduced risk of developing heart failure (OR = 0.45; p = 0.029, dominant model of inheritance), and a decrease in the left ventricular ejection fraction ≤ 40 % (OR = 0.43; p = 0.048 in the dominant model). The risk of reduced left ventricular ejection fraction in patients with heart failure is lower in carriers of the G allele of the Gln27Glu polymorphic locus of the β2-adrenergic receptor gene (OR = 0.52, p = 0.025, overdominant inheritance model).