ASSOCIATION BETWEEN TOLL-LIKE RECEPTOR GENES POLYMORPHISM (TLR2, TLR4, AND TLR6) AND SARS COV-2 INFECTION IN THE WEST SIBERIAN REGION OF RUSSIA



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Abstract

Abstract

The presence of preceding cardiovascular disease (CVD) is an important risk factor for the severe clinical course of COVID-19. In addition, COVID-19 is often aggravated by cardiovascular complications. The relationship between COVID-19 and the cardiovascular system is very complex and has not been studied. When infected with SARS-CoV-2, the innate immune response is activated through the toll-like receptors (TLRs) family. And TLR role in the pathogenesis of cardiovascular diseases is important. The aim of the study was to conduct the comprehensive comparative analysis by assessing toll-like receptor TLR2 (rs5743708), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810), TLR6 (rs5743810) gene polymorphism in COVID-19 convalescent patients to identify markers for disease susceptibility, severity of the course and development of cardiovascular complications. 260 patients with COVID-19 of varying severity degrees were examined. Groups with mild, moderate, and severe disease, groups with history of cardiovascular issues, and COVID-19 convalescent patients newly diagnosed with them were identified. Single nucleotide polymorphisms TLR2 (rs5743708), TLR4 (rs4986790, rs4986791), TLR6 (rs5743810) were analyzed by real-time PCR. Statistical was carried out by using SPSS 23.0 software. Gene allele and genotype rates were assessed by using a two-way Fisher criterion, and in cases of multiple comparisons, the Bonferroni correction. An increase of TLR2G and TLR2GG was revealed in COVID-19 patients. Heterozygosity in this position was significantly reduced in the group of patients. No differences in the frequencies of genotypes between groups with different disease severity was observed. TLR2-753 ArgArg:TLR4-299 AspGly:TLR4-399 ThrThr were decreased in patients with a combined moderate-severe vs. mild COVID-19. CVD patients with TLR4-299 AspAsp, TLR4-299 AspAsp:TLR4-399ThrThr were significantly more likely to suffer from severe COVID-19. The complex TLR4-299 AspGly:TLR4-399 ThrThr and TLR2-753 ArgArg:TLR4-299 AspGly:TLR4-399 ThrThr are associated with a milder disease course. Six complexes were identified, the frequency of which is significantly higher in COVID-19 convalescent patients with cardiovascular complications. These data confirm that the TLR polymorphism affects COVID-19 development and clinical diversity.

About the authors

Alla Shevchenko

Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL- Branch of IC&G SB RAS), Novosibirsk, Russian Federation

Email: shalla64@mail.ru
ORCID iD: 0000-0001-5898-950X

Leading Researcher, Laboratory of Clinical Immunogenetics

Россия

Viktor Prokofiev

Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL- Branch of IC&G SB RAS), Novosibirsk, Russian Federation

Email: vf_prok@mail.ru
ORCID iD: 0000-0001-7290-1631

MD, PhD, Senior Researcher, Laboratory of Clinical Immunogenetics RICEL- Branch of IC&G SB RAS

Россия

Vladimir Konenkov

Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL- Branch of IC&G SB RAS), Novosibirsk, Russian Federation

Email: vikonenkov@gmail.com
ORCID iD: 0000-0001-7385-6270

MD, PhD, Dr. Med. Sci., Professor, Academician of Russian Academy of Science, Head of the Laboratory of Clinical Immunogenetics RICEL- Branch of IC&G SB RAS

Россия

Alexandra Karaseva

Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IIPM - Branch of IC&G SB RAS), Novosibirsk, Russian Federation

Email: Sas96@bk.ru
ORCID iD: 0000-0002-0423-5021

Junior Researcher of the Laboratory of Genetic and Environmental Determinants of the Human Life Cycle IIPM — Branch of IC&G SB RAS

Россия

Alena Afanaseva

Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IIPM - Branch of IC&G SB RAS), Novosibirsk, Russian Federation

Email: alena.dmytryevna@yandex.ru
ORCID iD: 0000-0001-7875-1566

MD, PhD, head Laboratory of Genetic and Environmental Determinants of the Human Life Cycle IIPM — Branch of IC&G SB RAS

Россия

Irina Logvinenko

Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (IIPM - Branch of IC&G SB RAS), Novosibirsk, Russian Federation

Author for correspondence.
Email: 111157@mail.ru
ORCID iD: 0000-0003-1348-0253

Dr. Med. Sci., Professor, Chief Researcher of the Laboratory of Preventive Medicine IIPM — Branch of IC&G SB RAS

Россия

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