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

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 V. Shevchenko

Research Institute of Clinical and Experimental Lymphology — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

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

DSc (Biology), Leading Researcher, Laboratory of Clinical Immunogenetics

Russian Federation, Novosibirsk

V. F. Prokofiev

Research Institute of Clinical and Experimental Lymphology — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

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

PhD (Medicine), Leading Researcher, Laboratory of Clinical Immunogenetics

Russian Federation, Novosibirsk

V. I. Konenkov

Research Institute of Clinical and Experimental Lymphology — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

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

DSc (Medicine), Professor, RAS Full Member, Head of the Laboratory of Clinical Immunogenetics, Principal Investigator

Russian Federation, Novosibirsk

A. A. Karaseva

Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

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

Junior Researcher, Laboratory of Genetic and Environmental Determinants of the Human Life Cycle

Russian Federation, Novosibirsk

A. D. Afanaseva

Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

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

PhD (Medicine), Head of the Laboratory of Genetic and Environmental Determinants of the Human Life Cycle

Russian Federation, Novosibirsk

I. I. Logvinenko

Research Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

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

DSc (Medicine), Professor, Head Researcher, Laboratory of Preventive Medicine

Russian Federation, Novosibirsk

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