Polymorphism of TLR genes and the course of COVID-19 bilateral pneumonia

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Abstract

BACKGROUND: COVID-19 is a disease which course depends on a number of factors, including genetic ones, among which the genes of the innate immune system receptors – TLR (toll-like receptors), which play a central role in the development of innate immunity reactions, are of particular interest. The SARS-CoV-2 virus structure includes, in addition to the nucleocapsid, a protein-lipid membrane envelope, which determines the recognition of virus components by different TLRs, including TLR2 subfamily receptors (TLR1, 6, 10), which genetic polymorphisms occur with different frequencies in different human populations and affect not only the functional activity of the innate immunity but also determine the quality of the adaptive immune response.

AIM: The study aimed to determine the association of polymorphisms of toll-like receptor genes TLR1, TLR6 and TLR10 with the severity of coronavirus infection (COVID-19) in the Russian population of the Chelyabinsk region.

MATERIALS AND METHODS: The study included 86 patients from COVID-departments of hospitals in Chelyabinsk with a diagnosis of bilateral pneumonia with a degree of severity: moderate (M-BLP, n = 36) or severe (S-BLP, n = 50). The control group consisted of 100 healthy individuals from the register of the Chelyabinsk regional hemotransfusion station (“Control”). All the individuals studied belonged to the Russian ethnic group. Polymorphisms 1805T>G of TLR1 gene, 745C>T of TLR6 gene and 721A>C of TLR10 gene were determined using polymerase chain reaction with restriction fragment length polymorphism. The analysis of the association between genotypes and the status of individuals was carried out using the correspondence analysis and the Monte Carlo method.

RESULTS: It was revealed that the differences between the studied groups are completely determined by TLR1 genotypes. The GG genotype with statistical significance is more often detected in the “Control” group compared to M-BLP and S-BLP (p < 0.001, OR = 12.94) and can be assessed as protective in relation to the development of bilateral pneumonia in COVID-19. The TT genotype can be considered as predisposing to the development of a severe form of bilateral pneumonia in COVID-19 (p = 0.022): the TT genotype is significantly less common (OR = 0.20) in the M-BLP group compared to S-BLP.

CONCLUSIONS: It can be assumed that the genetic variant 1805*G of the TLR1 gene, which provides a moderate pro-inflammatory response and predominates in European populations, gives an advantage to its owners, preventing the development of complicated conditions in COVID-19 infection.

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About the authors

Alexander V. Evdokimov

Chelyabinsk State University

Author for correspondence.
Email: avdax@yandex.ru
ORCID iD: 0000-0002-7011-368X
SPIN-code: 9092-4429
Scopus Author ID: 56946405800
ResearcherId: ABA-8628-2021

Cand. Sci. (Biol.), Assistant Professor at the Department of Microbiology, Immunology and General Biology of the Biology Faculty

Russian Federation, 129, Bratiev Kashirinykh Str., Chelyabinsk, 454001

Tatyana A. Suslova

Chelyabinsk State University; Chelyabinsk Regional Hemotransfusion Station

Email: hla_chel@mail.ru
ORCID iD: 0000-0002-7028-6839
SPIN-code: 2869-1066

MD, Cand. Sci. (Med.), Assistant Professor, Head of the Laboratory of Immunological Research, Assistant Professor at the Department of Microbiology, Immunology and General Biology of the Biology Faculty

Russian Federation, 129, Bratiev Kashirinykh Str., Chelyabinsk, 454001; Chelyabinsk

Svetlana V. Belyaeva

Chelyabinsk State University; Chelyabinsk Regional Hemotransfusion Station

Email: shshvetlana@gmail.com
SPIN-code: 9485-3361

Cand. Sci. (Biol.), biologist of the Laboratory of Immunological Research, Assistant Professor at the Department of Microbiology, Immunology and General Biology of the Biology Faculty

Russian Federation, 129, Bratiev Kashirinykh Str., Chelyabinsk, 454001; Chelyabinsk

Alexandra L. Burmistrova

Chelyabinsk State University

Email: burmal@csu.ru
ORCID iD: 0000-0001-6462-9500
SPIN-code: 2374-7309

MD, Dr. Sci. (Med.), Professor, Head of the Department of Microbiology, Immunology and General Biology of the Biology Faculty

Russian Federation, 129, Bratiev Kashirinykh Str., Chelyabinsk, 454001

Darya S. Stashkevich

Chelyabinsk State University

Email: stashkevich_dary@mail.ru
SPIN-code: 6592-1469

Cand. Sci. (Biol.), Assistant Professor, Dean of the Biology Faculty

Russian Federation, 129, Bratiev Kashirinykh Str., Chelyabinsk, 454001

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Supplementary files

Supplementary Files
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1. Fig. 1. Contribution of different TLR1/TLR6/TLR10 genotypes combinations to the association with the BLP form. The dashed line marks the average level above which the contribution is considered significant

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2. Fig. 2. Biplot of correspondence analysis. The graph simultaneously shows both combinations of genotypes (only those that have made the greatest contribution to the association with the studied groups are depicted) and the groups themselves. M-BLP — moderate bilateral pneumonia; S-BLP — severe bilateral pneumonia

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Copyright (c) 2021 Evdokimov A.V., Suslova T.A., Belyaeva S.V., Burmistrova A.L., Stashkevich D.S.

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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