Association of rs4986790 and rs4986791 polymorphisms of the TLR4 gene with the risk of developing acute respiratory viral diseases: a meta-analysis

Background. Acute respiratory viral infection (ARVI) is one of the pressing medical and socio-economic problems, frequently occurring in all age groups worldwide. The most important viral etiologic agents are respiratory syncytial virus (RSV) and influenza virus. TLR4 is an innate immune receptor on the cell surface that recognizes pathogen-associated molecular patterns (PAMPs), including viral proteins, and triggers the production of type I interferons and proinflammatory cytokines to fight infection. Many studies have reported the effect of TLR4 Asp299Gly and Thr399Ile polymorphisms on the risk of developing ARVI, but no definitive conclusions have been made.

Aim: to investigate the association between the rs4986790 and rs4986791 polymorphisms of the Toll-like receptor (TLR4) gene and the development of ARVI.

Methods. A systematic literature search was performed using the PubMed, Google Scholar Search, and Russian Science Citation Index (RSCI) databases according to PRISMA 2020 guidelines. Pooled odds ratios with corresponding 95% confidence intervals were calculated for five genetic models. Data processing and construction of forest plots to assess the pooled results were performed in RevMan 5.4.

Results. The meta-analysis included 9 publications on the rs4986790 polymorphism and 5 on the rs4986791 polymorphism, that met the inclusion/exclusion criteria. Most of the articles combined studies of both polymorphisms. The sumple size of the main group for Asp299Gly was 1228, the control group – 8694, for Thr399Ile – 629 and 2858, respectively. The results included in the meta-analysis did not have significant heterogeneity among studies for all genetic models. The analyzed data showed that the studied polymorphisms were not associated with the risk of ARVI.

Conclusions. The study may be useful for better understanding the exact role of each component of innate and adaptive immunity in ARVI. These data, summarizing the positive, negative or absent correlation between ARVI and gene polymorphisms, provide important information on the mechanisms of viral infection and can help in the development of new vaccines and pharmacological treatment.

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