Genetic polymorphism of some genes of toll-like receptors in patients with influenza A (H3N2)

Abstract

Background. Among all infectious diseases that occur in the human population, only acute respiratory viral infections, including influenza, lead to massive outbreaks, often taking on the character of epidemics and pandemics. Polymorphism of cytokine genes can be both a factor of predisposition and resistance to infection, the development of the disease, and a long, complicated course of influenza.

Aim. Study of the genetic polymorphism of the genes of toll-like receptors rs5743708 (Arg753Gln, G2258A), TLR3 rs3775291 (Phe412Leu, C1234T), TLR4 rs4986790 (Asp299Gly, A896G), TLR4 rs4986791 (Thr399Ile, C1196T) in healthy individuals and in patients with influenza A(H3N2).

Material and methods. The study, using the continuous sampling method, included patients with influenza A (H3N2; 89 people) who were treated at the Regional Clinical Infectious Diseases Hospital in Chita during the epidemic seasons of 2016–2017 and 2017–2018. The control group consisted of 96 practically healthy donors. To analyze the polymorphism of the TLR2 rs5743708 (Arg753Gln, G2258A), TLR3 rs3775291 (Phe412Leu, C1234T), TLR4 rs4986790 (Asp299Gly, A896G), and TLR4 rs4986791 (Thr399Ile, C1196T) genes the method of polymerase chain reaction with electrophoretic detection using standard kits from Scientific and Production Company “Litekh” (Moscow) was applied. Statistical analysis was carried out in accordance with the principles of the International Committee of Medical Journal Editors and the “Statistical Analysis and Methods in the Published Literature” recommendations. Pearson's χ2 test was used for comparative evaluation of qualitative nominal data.

Results. Patients with influenza A (H3N2) more often had heterozygous TLR2 753Arg/Gln variants [χ2=8.26, p=0.02; odds ratio (OR) 3.00; 95% confidence interval (CI) 1.33–6.73], homozygous TLR3 412Leu/Leu variants (χ2=11.68, p=0.003; OR=2.39; 95% CI 1.04–3.61), heterozygous variants of TLR4 299Asp/Gly (χ2=6.97; p=0.03; OR=2.15; 95% CI 1.02–4.70) and 399Thr/Ile (χ2=8.39; p= 0.01; OR=2.30; 95% CI 1.06–4.88) compared with a group of healthy donors.

Conclusion. The genotypes 753Arg/Gln of the TLR2 gene, 412Leu/Leu of the TLR3 gene, 299Asp/Gly of the TLR4 gene, Thr399Ile of the TLR4 gene predispose to the development of influenza A (H3N2); carriage of genotypes 753Arg/Arg of the TLR2 gene, 412Phe/Phe of the TLR3 gene, 299Asp/Asp of the TLR4 gene, 399Thr/Thr of the TLR4 gene reduces the likelihood of the influenza A(H3N2) development.

Keywords

influenza / gene polymorphism / toll-like receptors

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