Comparative assessment of genetic polymorphism of Toll-like 2 and 6 receptors predisposing for non-specific ulcerative colitis and irritable bowel syndrome in Russians from Chelyabinsk Region

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Abstract

Ulcerative colitis and irritable bowel syndrome are multifactorial disorders with genetic predisposition. Recent studies suggest that the mucosal immune activation, increased intestinal permeability, and altered host-microbiota interactions may modulate innate immune response, thus contributing to immunopathogenesis of these diseases. Toll-like receptors (TLR) are considered to play the main role in genetic susceptibility to the conditions. The mechanisms for regulating activity of Toll-like receptors are represented by single-nucleotide gene polymorphisms (SNPs), thus producing allelotypes with different biological effects. Among all known TLRs, TLR2 is the most actively studied. The TLR2 gene is located on the long arm of the chromosome 4 and contains the genetic variant leading to the substitution of arginine for glutamine (Arg753Gln) in TLR2 protein. Meanwhile, the most studied SNP of TLR6 is located at the C745T position causing Pro249Ser amino acid substitution in the protein. The present work aimed for analysis of distribution of alleles, genotypes and haplotype combinations of the TLR2 and TLR6 SNPs, and their associations with predisposal for ulcerative colitis and irritable bowel syndrome in Russians from Chelyabinsk Region. The following methods were used in the study: isolation of DNA samples from whole blood, genotyping of the studied gene polymorphisms using PCR with electrophoretic detection. The frequencies of two-locus haplotypes formed by SNPs TLR2 – TLR6 were calculated with Arlequin ver 3.5 software. Comparison of two populational samples for predisposition to UC and IBS was carried out using standard immunogenetic criteria. Significance of differences was set at p ≤ 0.05. Results: Analysis of the data showed the association of specific alleles and genotypes, but not TLR2 – TLR6 haplotypes, with predisposition to the studied diseases. The Arg753Gln gene polymorphism of TLR2 was shown to be significant for a predisposition to ulcerative colitis, and SNP Pro249Ser TLR6 is associated with susceptibility to irritable bowel syndrome in Russians from the Chelyabinsk Region.

About the authors

D. S. Stashkevich

Chelyabinsk State University

Author for correspondence.
Email: stashkevich_dary@mail.ru

PhD (Biology), Associate Professor, Dean, Biological faculty

Russian Federation, Chelyabinsk

S. V. Belyaeva

Chelyabinsk State University

Email: stashkevich_dary@mail.ru

PhD (Biology), Associate Professor, Department of Microbiology, Immunology and General Biology, Biological faculty

Russian Federation, Chelyabinsk

A. V. Evdokimov

Chelyabinsk State University

Email: stashkevich_dary@mail.ru

PhD (Biology), Associate Professor, Department of Microbiology, Immunology and General Biology, Biological faculty

Russian Federation, Chelyabinsk

References

  1. Бурмистрова А.Л., Беляева С.В. Визуализация генетических комбинаций, участвующих в формировании воспалительного ответа при туберкулезе легких, методом канонического анализа соответствий // Вестник Челябинского государственного университета, 2015. № 21 (376). С. 12-16. [Burmistrova A.L., Belyaeva S.V. Visualization of genetic combinations involved in the formation of the inflammatory response in pulmonary tuberculosis by the method of canonical correspondence analysis. Vestnik Chelyabinskogo gosudarstvennogo universiteta = Bulletin of the Chelyabinsk State University, 2015, no. 21 (376), pp. 12-16. (In Russ.)]
  2. Евдокимов А.В., Бурмистрова А.Л., Суслова Т.А. Определение частоты распределения точкового полиморфизма 745С>Т гена TLR6 в популяциях нагайбаков и башкир Челябинской области // Российский иммунологический журнал, 2014. Т. 8 (17), № 3. С. 311-314. [Evdokimov A.V., Burmistrova A.L., Suslova T.A. Determination of the distribution frequency of point polymorphism 745C>T of the TLR6 gene in the populations of Nagaybaks and Bashkirs of the Chelyabinsk region. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2014, Vol. 8 (17), no. 3, pp. 311-314. (In Russ.)]
  3. Сташкевич Д.С., Бурмистрова А.Л. Генетический полиморфизм толл-подобного рецептора 2 у больных ревматоидным артритом русской популяции Челябинской области // Российский иммунологический журнал, 2019. Т. 13, № 3. С. 1289-1292. [Stashkevich D.S., Burmistrova A.L. Genetic polymorphism of toll-like receptor 2 in patients with rheumatoid arthritis of the Russian population of the Chelyabinsk region. Rossiyskiy immunologicheskiy zhurnal = Russian Journal of Immunology, 2019, Vol. 13, no. 3, pp. 1289-1292. (In Russ.)]
  4. Belmonte L., Beutheu Youmba S., Bertiaux-Vandaële N., Antonietti M., Lecleire S., Zalar A., Gourcerol G., Leroi A.-M., Déchelotte P., Coëffier M., Ducrotté P. Role of toll like receptors in irritable bowel syndrome: differential mucosal immune activation according to the disease subtype. PLoS One, 2012. Vol. 7, no. 8, e42777. doi: 10.1371/journal.pone.0042777.
  5. Cheng Y., Zhu Y., Huang X., Zhang W., Han Z., Liu S. Association between TLR2 and TLR4 gene polymorphisms and the susceptibility to inflammatory bowel disease: A meta-analysis. PLoS One, 2015. Vol. 10, no. 5, e0126803. doi: 10.1371/journal.pone.0126803.
  6. Dorofeyev A.E., Dorofeyeva A.A., Kiriyan E.A., Rassokhina O.A., Dynia Y.Z. Genetic polymorphism in patients with early and late onset of ulcerative colitis. Wiad Lek, 2020, Vol. 73, no. 1, pp. 87-90.
  7. Excoffier L., Slatkin M. Maximum-likelihood estimation of molecular haplotype frequencies in a diploid population. Mol. Biol. Evol., 1995, Vol. 12, no. 5, pp. 921-927.
  8. Hu Y., Ye Z., Wu M., She Y., Li L., Xu Y., Qin K., Hu Z., Yang M., Lu F., Ye Q. The communication between intestinal microbiota and ulcerative colitis: an exploration of pathogenesis, animal models, and potential therapeutic strategies. Front. Med. (Lausanne), 2021, Vol. 8, 766126. doi: 10.3389/fmed.2021.766126.
  9. Jaen O., Petit-Teixeira E., Kirsten H., Ahnert P., Semerano L., Pierlot C., Cornelis F., Boissier M.-C., Falgarone G., European Consortium on Rheumatoid Arthritis Families. No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis. Arthritis Res. Ther., 2009. Vol. 11, no. 1, R5. doi: 10.1186/ar2589.
  10. SNPStats your web tool for SNP analysis. Available at: https://www.snpstats.net/start.htm [Date of access 15.05.2022].
  11. Wang H., Zhou S., Zhang J., Lei S., Zhou J. Correlations between TLR polymorphisms and inflammatory bowel disease: a meta-analysis of 49 case-control studies. Immunol. Res., 2019, Vol. 67, no. 1, pp. 142-150.
  12. Zhang Y., Jiang T., Yang X., Xue Y., Wang C., Liu J., Zhang X., Chen Z., Zhao M., Li J.C. Toll-like receptor -1, -2, and -6 polymorphisms and pulmonary tuberculosis susceptibility: a systematic review and meta-analysis. PLoS One, 2013, Vol. 8, no. 5, e63357. doi: 10.1371/journal.pone.0063357.

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Copyright (c) 2022 Stashkevich D.S., Belyaeva S.V., Evdokimov A.V.

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