Comparing the Frequency of TIM-3 Polymorphism in Multiple Sclerosis Patients with Healthy Controls

Document Type : مقاله کوتاه

Authors

1 MSc Student, Department of Immunology, School of Medicine AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

2 Assistant Professor, Cellular and Molecular Immunology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Associate Professor, Department of Cellular and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Assistant Professor, Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

5 PhD Student, Department of Genetics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

6 Professor, Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) initiated and mediated by autoreactive T-helper1 cells directed against myelin antigens. One of the T-cell surface receptors is T-cell immunoglobulin and mucin domain (TIM) family. There are several single nucleotide polymorphisms (SNPs) in their sequences witch had associated with susceptibility to different autoimmune diseases. The aim of this study was to investigate the susceptibility of patients with multiple sclerosis in Isfahan population, Iran, with polymorphism +4259A>C in TIM-3 gene.Methods: Blood samples were collected. DNA was extracted from the blood samples using Genomic DNA Extraction Kit. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was performed. TIM-3 gene was amplified using PCR. Then, the products were digested with restriction enzyme, PstI. Electrophoresis was performed for separating the digested products.Findings: Genotype and allele carrier frequency between patient and healthy groups were statistically significant (P = 0.029). The odds ratio of susceptibility to multiple sclerosis for whom carrying C allele of TIM-3, compared with those who do not carry, was about 2 (P = 0.010).Conclusion: +4259A>C polymorphism in TIM-3 gene is associated with multiple sclerosis in Isfahan population, measuring the expression level of the genes carrying such polymorphisms and their relevant protein functional and/or structural analysis could be helpful.

Keywords

References

  1. Bahreini SA, Jabalameli MR, Saadatnia M, Zahednasab H. The role of non-HLA single nucleotide polymorphisms in multiple sclerosis susceptibility. J Neuroimmunol 2010; 229(1-2): 5-15.
  2. Springer TA. Adhesion receptors of the immune system. Nature 1990; 346(6283): 425-34.
  3. Koguchi K, Anderson DE, Yang L, O'Connor KC, Kuchroo VK, Hafler DA. Dysregulated T cell expression of TIM3 in multiple sclerosis. J Exp Med 2006; 203(6): 1413-8.
  4. Rodriguez-Manzanet R, DeKruyff R, Kuchroo VK, Umetsu DT. The costimulatory role of TIM molecules. Immunol Rev 2009; 229(1): 259-70.
  5. Zhao W, Li Y, Wang Z, Li K, Yang S. Molecular characterization of the porcine TIM-3 gene. Scand J Immunol 2011; 73(1): 29-35.
  6. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol 2005; 6(12): 1245-52.
  7. Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, et al. TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. Eur J Immunol 2009; 39(9): 2492-501.
  8. Anderson AC, Anderson DE. TIM-3 in autoimmunity. Curr Opin Immunol 2006; 18(6): 665-9.
  9. Meyers JH, Sabatos CA, Chakravarti S, Kuchroo VK. The TIM gene family regulates autoimmune and allergic diseases. Trends Mol Med 2005; 11(8): 362-9.
  10. Lee J, Phong B, Egloff AM, Kane LP. TIM polymorphisms--genetics and function. Genes Immun 2011; 12(8): 595-604.
  11. Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH. TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev 2010; 235(1): 172-89.
  12. Chae SC, Park YR, Shim SC, Yoon KS, Chung HT. The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis. Immunol Lett 2004; 95(1): 91-5.
  13. Song YW, Im CH, Park JH, Lee YJ, Lee EY, Lee EB, et al. T-cell immunoglobulin and mucin domain 3 genetic polymorphisms are associated with rheumatoid arthritis independent of a shared epitope status. Hum Immunol 2011; 72(8): 652-5.
  14. Xu J, Yang Y, Liu X, Wang Y. The -1541 C>T and +4259 G>T of TIM-3 polymorphisms are associated with rheumatoid arthritis susceptibility in a Chinese Hui population. Int J Immunogenet 2011; 38(6): 513-8.
  15. Etemadifar M, Abtahi SH. Multiple sclerosis in Isfahan, Iran: Past, Present and Future. Int J Prev Med 2012; 3(5): 301-2.
  16. Khademi M, Illes Z, Gielen AW, Marta M, Takazawa N, Baecher-Allan C, et al. T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid-derived mononuclear cells in multiple sclerosis. J Immunol 2004; 172(11): 7169-76.
  17. Nuchnoi P, Ohashi J, Kimura R, Hananantachai H, Naka I, Krudsood S, et al. Significant association between TIM1 promoter polymorphisms and protection against cerebral malaria in Thailand. Ann Hum Genet 2008; 72(Pt 3): 327-36.
  18. Kane LP. T cell Ig and mucin domain proteins and immunity. J Immunol 2010; 184(6): 2743-9.
  19. Su EW, Lin JY, Kane LP. TIM-1 and TIM-3 proteins in immune regulation. Cytokine 2008; 44(1): 9-13.
  20. Yang L, Anderson DE, Kuchroo J, Hafler DA. Lack of TIM-3 immunoregulation in multiple sclerosis. J Immunol 2008; 180(7): 4409-14.
  21. Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, et al. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 2002; 415(6871): 536-41.
Journal of Isfahan Medical School
Volume 33, Issue 341 - Serial Number 341
May and June 2015
Pages 1066-1075

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History

  • Receive Date: 26 April 2015
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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