The role of Toll-like receptor 4 gene polymorphism in the development of organ dysfunction in patients with severe pneumonia associated with A/H1N1 influenza

Abstract

The aim of the study. To identify the frequency of occurrence of TLR4 Asp299Gly (rs4986790) gene polymorphism and to establish its contribution to the development of organ dysfunction in patients with severe pneumonia associated with A/H1N1 influenza.Materials and methods. The study included 55 patients with severe pneumonia associated with A/H1N1 influenza. Inclusion criteria: severe pneumonia; consolidation/ground-glass syndrome according to chest X-ray/CT. Exclusion criteria: unstable hemodynamics; body mass index > 30; diabetes mellitus; HIV; tuberculosis, oncopathology. Verification of the pathogen in the respiratory swab was carried out using PCR method: A/H1N1 influenza virus RNA was identified. The age of the patients was 47 [38; 62] years. Among all the patients the proportion of men was 47.8 %, of women – 52.2 %. Patients were divided into 2 groups: group 1 included patients with SOFA scale (Sequential Organ Failure Assessment) score ≥ 2 points; group 2 – patients with SOFA scale score ˂ 2 points. Gene SNPs were determined by PCR method using standard kits developed by Research and Production Company “Litekh” (Moscow). Amplification of the TLR4 gene fragments was carried out in a thermocycler Bis-M111 (Bis-N LLC, Novosibirsk). Genomic DNA isolated from whole blood leukocytes using the “DNA Express Blood” reagent was analyzed followed by an amplification reaction. The amplification product was detected in a 3% agarose gel.Results. Multiple organ dysfunction (SOFA scale score ≥ 2 points) in patients with severe pneumonia associated with A/H1N1 influenza was registered in 24 (43.6 %) cases. When analyzing the frequency of occurrence of the minor Gly allele, according to genetic models, the differences were established between patients of the groups 1 and 2 in codominant (p = 0.023; odds ratio (OR) – 8.82 (0.95–81.89)) and dominant (p = 0.005; OR = 12.35 (1.40–109.07)) models.Conclusion. Severe pneumonia associated with A/H1N1 influenza is accompanied by a high incidence of organ dysfunction. The risk of organ failure development is 2.1 times increased in patients with severe pneumonia with identified TLR4 Asp299Gly gene polymorphism, which probably requires further study.