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Received date: 19/05/2025 Published date: 03/06/2025 Case Report

Influence of TOLL-LIKE Receptor Polymorphisms on Susceptibility to Covid-19

Ashchina L.A^1*, Baranova N.I¹, Lesina O.N¹, Mikuliak N.I²

¹Penza Institute for Further Training of Physicians – Branch Campus of the Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuing Professional Education" of the Ministry of Healthcare of the Russian Federation, 8A Stasova St., Penza, 440060, Russian Federation
²Penza State University, Medical Institute, 40 Krasnaya St., Penza, 440026, Russian Federation.

*Corresponding author

Aschina LA, Penza Institute for Further Training of Physicians – Branch Campus of the Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuing Professional Education" of the Ministry of Healthcare of the Russian Federation, 8A Stasova St., Penza, 440060, Russian Federation

DOI: 10.55920/JCRMHS.2025.11.001475

Abstract

COVID-19 is a disease caused by SARS-CoV-2 virus and has affected the lives of millions of people. We examined 172 patients with COVID-19 and 40 healthy donors for TLR2 (rs574708), TLR4 (rs4986790), TLR4 (rs4986791), TLR7 (rs3853839) polymorphisms to identify possible markers of disease susceptibility.

Introduction

COVID-19 is a disease caused by the SARS-CoV-2 virus. Toll-like receptors (TLRs) are responsible for recognition of viral particles and activation of the innate immune system, and play an important role in susceptibility to COVID-19. TLRs have been shown to be involved in the cytokine storm characteristic of severe COVID-19, and different expression patterns have been associated with COVID-19 progression [1]. For example, TLR3 expression was lower in patients with severe COVID-19 compared to patients with mild COVID-19. In addition, TLR4 expression was higher in patients with COVID-19 [2]. The role of TLR 2, 4, 7, 8, and 9 polymorphisms is known in patients with COVID-19 who required hospitalisation. Thus, genetic differences between individuals may influence their susceptibility and resistance to the disease. There are several studies investigating the role of genetic polymorphisms and COVID-19 [3,4,5]. However, the contribution of TLR polymorphisms to susceptibility to SARS-CoV-2 infection remains unclear to date.

The aim of the study was to investigate the polymorphism of TLR2 (rs574708), TLR4 (rs4986790), TLR4 (rs4986791), TLR7 (rs3853839) genes in COVID-19 patients and controls.

Material and Methods

The polymorphisms of TLR2 (rs574708), TLR4 (rs4986790), TLR4 (rs4986791), TLR7 (rs3853839) were studied in 172 COVID-19 patients and 40 healthy subjects by polymerase chain reaction with real-time detection of the results. The χ2 criterion with Yates correction was used to assess the difference between groups on qualitative grounds, and the two-sided Fisher's criterion (PF) was used when its applicability conditions were violated. The strength of associations was assessed in the values of the odds ratio odds ratio (OR) and 95% confidence interval.

Results

The study of TLR2 (rs574708) in the groups of patients and healthy people showed a difference in the frequency of genotypes, namely, patients had a higher frequency of GG genotype and a lower frequency of AG genotype compared to the control group. The rs5743708 TLR2 genetic polymorphism has been shown to affect the intracellular signalling function of TLR2 and may alter cytokine production in patients with COVID-19. Analysis of the rs4986790 polymorphism in the TLR4 gene showed a significantly higher frequency of the GG genotype and a lower frequency of the AA genotype in COVID-19 patients compared with the control group. The study of genotype frequencies of TLR4 polymorphism (rs4986791) showed significantly higher frequency of TC and TT genotype and lower frequency of CC genotype in the group of COVID-19 patients compared to healthy people. The SARS-CoV-2 spike protein has been shown to bind to TLR4, activating the MyD88 signalling pathway and triggering the production of pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α. The rs4986790 and rs4986791 polymorphisms in the TLR4 gene may affect the extracellular domain by reducing ligand binding and protein interactions. TLR7 polymorphism analysis (rs3853839) revealed, between COVID-19 patients and healthy individuals, a significantly higher frequency of GG genotype and a lower frequency of GC genotype in patients. It is known that the TLR7 gene is encoded on the X-chromosome and the TLR7 receptor recognises fragments of single-stranded RNA and is localised in endosomes. In response to viral infections TLR7 mediates the production of type I interferons and antiviral cytokines. This receptor has been shown to be activated in patients infected with SARS-CoV-2.

Conclusions

Thus, higher frequencies of occurrence of genotypes GG of TLR2 gene (rs574708), GG of TLR4 gene (rs4986790) were found in COVID-19 patients compared to the control group, TC and TT of TLR4 gene (rs4986791), GG of TLR7 gene (rs3853839), and lower frequencies of occurrence of genotypes AG of TLR2 gene (rs574708), AA of TLR4 gene (rs4986790), CC of TLR4 gene (rs4986791), GC of TLR7 gene (rs3853839). The results obtained may contribute to the understanding of the immunogenetics of COVID-19 and may also be used as possible markers of susceptibility to this disease.

References

Journal of Clinical Case Reports, Medical Images and Health Sciences (ISSN 2832-1286) is a peer-reviewed journal dedicated to publishing clinical images from all sectors of medicine. The goal of this magazine is to disseminate information about new discoveries and treatments in science and medicine.

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