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IL6R Gene Polymorphic Variant rs2228145(C >A) as a Marker of Genetic Liability to Nonalcoholic Steatohepatitis in the Russian Population of Karelia

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Bulletin of Experimental Biology and Medicine Aims and scope

Association of IL6R gene polymorphic variant rs2228145(C>A) with the development of nonalcoholic steatohepatitis in Karelia residents is detected. The risk of nonalcoholic steatohepatitis is more than 2-fold higher in carriers of CC genotype by rs2228145 polymorphic marker than in carriers of other genotypes. Plasma levels of IL-6 and the content of IL6R gene transcripts in the peripheral blood leukocytes are higher in patients with nonalcoholic steatohepatitis than in normal subjects. No relationships between rs2228145 polymorphism and the level of IL-6 and content of IL6 and IL6R mRNA were detected. Gene IL6R polymorphic variant rs2228145(C>A) seems to be involved in genetic predisposition of the population of Karelia to nonalcoholic steatohepatitis. However, biochemical and molecular mechanisms underlying the relationship of rs2228145 with the development of nonalcoholic steatohepatitis are not yet studied.

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References

  1. Fletcher RH, Fletcher SW, Wagner EK. Clinical Epidemiology: The Essentials. Moscow, 1998. Russian.

  2. Braunersreuther V, Viviani G.L, Mach F, Montecucco F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J. Gastroenterol. 2012;18(8):727-735.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Ferreira RC, Freitag DF, Cutler AJ, Howson JM, Rainbow DB, Smyth DJ, Kaptoge S, Clarke P, Boreham C, Coulson RM, Pekalski ML, Chen WM, Onengut-Gumuscu S, Rich SS, Butterworth AS, Malarstig A, Danesh J, Todd JA. Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. PLoS Genet. 2013;9(4):e1003444. doi: https://doi.org/10.1371/journal.pgen.1003444.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E, Roka R, Schernthaner G. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler. Thromb. Vasc. Biol. 2003;23(6):1042-1047.

    Article  PubMed  CAS  Google Scholar 

  5. Krook A. IL-6 and metabolism-new evidence and new questions. Diabetologia. 2008;51(7):1097-1099.

  6. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-408.

    Article  PubMed  CAS  Google Scholar 

  7. Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S. Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc. Natl Acad. Sci. USA. 1993;90(21):10,193-10,197.

  8. Pinto Lde F, Compri C.M, Fornari JV, Bartchewsky W, Cintra DE, Trevisan M, Carvalho Pde O, Ribeiro ML, Velloso LA, Saad MJ, Pedrazzoli J Jr, Gambero A. The immunosuppressant drug, thalidomide, improves hepatic alterations induced by a high-fat diet in mice. Liver Int. 2010;30(4):603-610.

    Article  PubMed  CAS  Google Scholar 

  9. Polgár A, Brózik M, Tóth S, Holub M, Hegyi K, Kádár A, Hodinka L, Falus A. Soluble interleukin-6 receptor in plasma and in lymphocyte culture supernatants of healthy individuals and patients with systemic lupus erythematosus and rheumatoid arthritis. Med. Sci. Monit. 2000;6(1):13-18.

    PubMed  Google Scholar 

  10. Rafiq S, Frayling TM, Murray A, Hurst A, Stevens K, Weedon MN, Henley W, Ferrucci L, Bandinelli S, Corsi AM, Guralnik JM, Melzer D. A common variant of the interleukin 6 receptor (IL-6r) gene increases IL-6r and IL-6 levels, without other inflammatory effects. Genes Immun. 2007;8(7):552-559.

  11. Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S. The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim. Biophys. Acta. 2011;1813(5):878-888.

    Article  PubMed  CAS  Google Scholar 

  12. Streetz KL, Tacke F, Leifeld L, Wüstefeld T, Graw A, Klein C, Kamino K, Spengler U, Kreipe H, Kubicka S, Müller W, Manns MP, Trautwein C. Interleukin 6/gp130-dependent pathways are protective during chronic liver diseases. Hepatology. 2003;38(1):218-229.

  13. van Dongen J, Jansen R, Smit D, Hottenga JJ, Mbarek H, Willemsen G, Kluft C; AAGC Collaborators, Penninx BW, Ferreira MA, Boomsma DI, de Geus EJ. The contribution of the functional IL6R polymorphism rs2228145, eQTLs and other genome-wide SNPs to the heritability of plasma sIL-6R levels. Behav. Genet. 2014;44(4):368-382.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wang F, Xu L, Feng X, Guo D, Tan W, Zhang M. Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis. Arthritis Res. Ther. 2012;14(5):R228. doi: https://doi.org/10.1186/ar4067.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am. J. Gastroenterol. 2008;103(6):1372-1379.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to L. V. Topchieva.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 165, No. 1, pp. 75-79, January, 2018

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Topchieva, L.V., Kurbatova, I.V., Dudanova, O.P. et al. IL6R Gene Polymorphic Variant rs2228145(C >A) as a Marker of Genetic Liability to Nonalcoholic Steatohepatitis in the Russian Population of Karelia. Bull Exp Biol Med 165, 64–68 (2018). https://doi.org/10.1007/s10517-018-4100-3

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  • DOI: https://doi.org/10.1007/s10517-018-4100-3

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