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Research Article
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Association between Multiple Sclerosis and FOXP3 Gene Promoter Region Mutations

Year 2018, Volume: 40 Issue: 3, 226 - 232, 30.09.2018

Nilgun Cekin , Ergun Pinarbasi , Aslihan Esra Bildirici Seyda Akin Ozlem Kayim Yildiz

https://doi.org/10.7197/223.vi.419261
Cited By: 2

Abstract

Regulatory T-Cells (Treg Cells), as
one of the immune system components, have been highly effective in the
autoimmune diseases prevention, particularly multiple
sclerosis (MS). MS is a chronic inflammatory and autoimmune disease characterized by immune
infiltration and inflammation in the central nervous system. Regulatory T
(Treg) cells play an important role in the control of autoimmunity. Expression
and action of the transcription factor FOXP3
controls the development and
function of Treg cell. The aim of this study was to investigate the association
between MS and FOXP3 gene promoter
region polymorphisms rs2232365 (-924A/G) and rs3761548 (-3279A/C) in a Turkish
population. In this case-control study we investigated these polymorphisms in 80
MS patients and 80 healthy controls using PCR-RFLP methods.



Results of our study showed
that while there is significant correlation between MS and FOXP3 rs3761548 polymorphism (p=0.031), FOXP3 rs2232365 polymorphism, has not been found to be associated
with the disease (p=0.31).  As FOXP3 gene is one of the most important genes in the regulation
of the immune cells, it may be concluded that the expression of this gene is
important in MS patients. As this SNP is located in the promoter region of the
gene, it may affect the expression level of FOXP3
protein.

Keywords

Multiple sclerosis FOXP3 polymorphism

References

  • 1. Hafler DA, Slavik JM, Anderson DE, O’Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol Rev, 2005; 204:208-231.
  • 2. İdiman E. Multipl skleroz’un immünopatogenezi. Türkiye Klinikleri J Neur, 2004; 2:171-176.
  • 3. Weissert R. The immune pathogenesis of Multiple sclerosis. Pharmacol, 2013; 8:857-866.
  • 4. Piccirillo AC, Shevach ME. Naturally occuring CD4(+)CD25(+) immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol, 2004; 16(2):81-88.
  • 5. Işık N, Yıldız-Manukyan N, Aydın-Cantürk İ, Candan F, Ünsal-Çakmak A, Saruhan-Direskeneli G. Multipl skleroza genetik yatkınlık: Foxp3 gen polimorfizmin rolü. Nöropsikiyatri Arşivi, 2014; 51:69-73.
  • 6. Singer BD, King LS, D’Alessio FR. Regulatory T cells as immunotherapy. Front Immunol, 2014; 5:46.
  • 7. Viglietta V, Baecher-Allan C, Weiner HI, Hafler DA. Loss of functional supression by CD4+CD25+ regulatory T cells from patients with Multiple sclerosis. J Exp Med, 2004; 199:971-979.
  • 8. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S. Advances in the immunopathogenesis of Multiple sclerosis. Curr Opin Neurol, 2015; 28:206-219.
  • 9. Aranami T, Yamamura T. Th17 cells and autoimmune encephalomyelitis (EAE/MS). Allergo Int, 2008; 57:115-120.
  • 10. Dendrou CA, Fugger L, Friese MA. Immunopathology of Multiple sclerosis. Nat Rev Immunol, 2015; 15:545-558.
  • 11. Bos SD, Berge T, Cellus EG, Harbo HF. From genetic associations to functional studies in Multiple sclerosis. Eur J Neurol, 2016; 23:847-853.
  • 12. Chang D, Gao F, Slavney A, Ma L, Waldman YY, Sams AJ, et al. Accounting for eXentricties: analysisof the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases. Plos One, 2014; 9:e113684.
  • 13. Hollenbach JA, Oksenberg JR. The immunogenetics of Multiple sclerosis: A comprehensive review. J Autoimmun, 2015; 64:13-25.
  • 14. Oda JMM, Hirata BKB, Guembarovski RL, Watanabe MAE. Genetic polymorphism in FOXP3 gene: imbalance in regulatory T-cell role and development of human diseases. J.Genet. 2013; 92:163–171.
  • 15. Katoh H, Zheng P, Liu Y. Foxp3: genetic and epigenetic implications for autoimmunity. J Autoimmun, 2013; 41:72-78.
  • 16. Marques CR, Costa GN, da Silva TM, Telxira TO, de Andrade EM, et al. Genetic and epigenetic studies of Foxp3 in asthma and allergy. Asthma Res Pract, 2015; 1:10.
  • 17. Gajdosechova B, Javor J, Cierny D, Michalik J, Durmanova V, Shawkatova I, Parnicka Z, et al. Association of Foxp3 polymorphisms rs3761547 and rs3761548 with Multiple sclerosis in the Slovak population. Act Nerv Super Rediviva, 2017; 59(1):9-15.
  • 18. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for Multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol, 2005; 58:840-846.
  • 19. Ullrich A, Shine J, Chirgwin J, et al. Rat insülin genes: construction of plasmids containing the coding sequences. Science, 1977; 196(4296):1313-1319.
  • 20. International Multiple Sclerosis Genetic Consortium (IMSGC), Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppien A, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for Multiple sclerosis. Nat Genet, 2013; 45:1353-1360.
  • 21. Graber J, McGraw C, Kimbrough D, Dhib-Jalbut S. Overlapping and distinct mechanisms of action of Multiple sclerosis therapies. Clin Neurol Neurosurg, 2010; 112:583-591.
  • 22. Men M, Kutlu C, İlhan-Algın D, Gülbaş Z. The Cd4(+)Cd25(+) regulatory T cell profile and Foxp3 expression and clinic associations of in various stage and types of Multiple sclerosis. Osmangazi Journal of Medicine, 2018; 40(1):7-13.
  • 23. Coffer PJ, Burgering BMT. Forkhead-box transcription factors and their role in the immune system. Nat Rev, 2004; 4:889-899.
  • 24. Gagliani N, Jofra T, Valle A, Stabilini A, Morsiani C, Gregori S, Deng S, Rothstein DM, Arkinson M, Kamanaka M, Flavell RA, Roncarolo MG, Battaglia M. Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen. Am J Transplant, 2013; 13(8):1963-75.
  • 25. Koyama M, Kuns RD, Olver SD, Lineburg KE, Lor M, Teal BE, Raffelt NC, Levegue L, Chan CJ, et al. Promoting regulation via the inhibition of DNAM-1 after transplantation. Blood, 2013; 121(17):35111-20.
  • 26. Huan J, Culbertson N, Spencer L, Bartholomew R, Burrows GG, Chou YK, Bourdette D, Ziegler SF, Offner H, Vandenbark AA. Decreased Foxp3 levels in Multiple sclerosis patients. Journal of Neuroscience Research, 2005; 81:45-52.
  • 27. Jafarzadeh A, Jamali M, Mahdavi R, Ebrahimi HA, Hajghani H, Khosravimashizi A, Nemati M, Najafipour H, Sheikhi A, Mohammadi MM, Daneshvar H. Circulating levels of interleukin-35 in patients with Multiple sclerosis: evaluation of the influences of Foxp3 gene polymorphsism and treatment program. J Mol Neurosci, 2015; 55:891-897.
  • 28. Efekharian MM, Sayad A, Omrani MD, Ghannad MS, Noroozi R, Mazdeh M, et al. Single nucleotide polymorphisms in the Foxp3 gene are associated with incrased risk of relapsing-remitting multiple sclerosis. Hum Antibodies, 2016; doi: 10.3233/HAB-160299.
  • 29. Gholami M, Darvish H, Ahmadi H, Rahimi-Aliabadi S, Emamalizadeh B, Eslami Amirabadi MR, et al. Functional genetic variants of Foxp3 and risk of multiple sclerosis. Iran Red Crescent Med J, 2016; e34597.

Year 2018, Volume: 40 Issue: 3, 226 - 232, 30.09.2018

Nilgun Cekin , Ergun Pinarbasi , Aslihan Esra Bildirici Seyda Akin Ozlem Kayim Yildiz

https://doi.org/10.7197/223.vi.419261
Cited By: 2

Abstract

References

  • 1. Hafler DA, Slavik JM, Anderson DE, O’Connor KC, De Jager P, Baecher-Allan C. Multiple sclerosis. Immunol Rev, 2005; 204:208-231.
  • 2. İdiman E. Multipl skleroz’un immünopatogenezi. Türkiye Klinikleri J Neur, 2004; 2:171-176.
  • 3. Weissert R. The immune pathogenesis of Multiple sclerosis. Pharmacol, 2013; 8:857-866.
  • 4. Piccirillo AC, Shevach ME. Naturally occuring CD4(+)CD25(+) immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol, 2004; 16(2):81-88.
  • 5. Işık N, Yıldız-Manukyan N, Aydın-Cantürk İ, Candan F, Ünsal-Çakmak A, Saruhan-Direskeneli G. Multipl skleroza genetik yatkınlık: Foxp3 gen polimorfizmin rolü. Nöropsikiyatri Arşivi, 2014; 51:69-73.
  • 6. Singer BD, King LS, D’Alessio FR. Regulatory T cells as immunotherapy. Front Immunol, 2014; 5:46.
  • 7. Viglietta V, Baecher-Allan C, Weiner HI, Hafler DA. Loss of functional supression by CD4+CD25+ regulatory T cells from patients with Multiple sclerosis. J Exp Med, 2004; 199:971-979.
  • 8. Yadav SK, Mindur JE, Ito K, Dhib-Jalbut S. Advances in the immunopathogenesis of Multiple sclerosis. Curr Opin Neurol, 2015; 28:206-219.
  • 9. Aranami T, Yamamura T. Th17 cells and autoimmune encephalomyelitis (EAE/MS). Allergo Int, 2008; 57:115-120.
  • 10. Dendrou CA, Fugger L, Friese MA. Immunopathology of Multiple sclerosis. Nat Rev Immunol, 2015; 15:545-558.
  • 11. Bos SD, Berge T, Cellus EG, Harbo HF. From genetic associations to functional studies in Multiple sclerosis. Eur J Neurol, 2016; 23:847-853.
  • 12. Chang D, Gao F, Slavney A, Ma L, Waldman YY, Sams AJ, et al. Accounting for eXentricties: analysisof the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases. Plos One, 2014; 9:e113684.
  • 13. Hollenbach JA, Oksenberg JR. The immunogenetics of Multiple sclerosis: A comprehensive review. J Autoimmun, 2015; 64:13-25.
  • 14. Oda JMM, Hirata BKB, Guembarovski RL, Watanabe MAE. Genetic polymorphism in FOXP3 gene: imbalance in regulatory T-cell role and development of human diseases. J.Genet. 2013; 92:163–171.
  • 15. Katoh H, Zheng P, Liu Y. Foxp3: genetic and epigenetic implications for autoimmunity. J Autoimmun, 2013; 41:72-78.
  • 16. Marques CR, Costa GN, da Silva TM, Telxira TO, de Andrade EM, et al. Genetic and epigenetic studies of Foxp3 in asthma and allergy. Asthma Res Pract, 2015; 1:10.
  • 17. Gajdosechova B, Javor J, Cierny D, Michalik J, Durmanova V, Shawkatova I, Parnicka Z, et al. Association of Foxp3 polymorphisms rs3761547 and rs3761548 with Multiple sclerosis in the Slovak population. Act Nerv Super Rediviva, 2017; 59(1):9-15.
  • 18. Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS. Diagnostic criteria for Multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol, 2005; 58:840-846.
  • 19. Ullrich A, Shine J, Chirgwin J, et al. Rat insülin genes: construction of plasmids containing the coding sequences. Science, 1977; 196(4296):1313-1319.
  • 20. International Multiple Sclerosis Genetic Consortium (IMSGC), Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppien A, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for Multiple sclerosis. Nat Genet, 2013; 45:1353-1360.
  • 21. Graber J, McGraw C, Kimbrough D, Dhib-Jalbut S. Overlapping and distinct mechanisms of action of Multiple sclerosis therapies. Clin Neurol Neurosurg, 2010; 112:583-591.
  • 22. Men M, Kutlu C, İlhan-Algın D, Gülbaş Z. The Cd4(+)Cd25(+) regulatory T cell profile and Foxp3 expression and clinic associations of in various stage and types of Multiple sclerosis. Osmangazi Journal of Medicine, 2018; 40(1):7-13.
  • 23. Coffer PJ, Burgering BMT. Forkhead-box transcription factors and their role in the immune system. Nat Rev, 2004; 4:889-899.
  • 24. Gagliani N, Jofra T, Valle A, Stabilini A, Morsiani C, Gregori S, Deng S, Rothstein DM, Arkinson M, Kamanaka M, Flavell RA, Roncarolo MG, Battaglia M. Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen. Am J Transplant, 2013; 13(8):1963-75.
  • 25. Koyama M, Kuns RD, Olver SD, Lineburg KE, Lor M, Teal BE, Raffelt NC, Levegue L, Chan CJ, et al. Promoting regulation via the inhibition of DNAM-1 after transplantation. Blood, 2013; 121(17):35111-20.
  • 26. Huan J, Culbertson N, Spencer L, Bartholomew R, Burrows GG, Chou YK, Bourdette D, Ziegler SF, Offner H, Vandenbark AA. Decreased Foxp3 levels in Multiple sclerosis patients. Journal of Neuroscience Research, 2005; 81:45-52.
  • 27. Jafarzadeh A, Jamali M, Mahdavi R, Ebrahimi HA, Hajghani H, Khosravimashizi A, Nemati M, Najafipour H, Sheikhi A, Mohammadi MM, Daneshvar H. Circulating levels of interleukin-35 in patients with Multiple sclerosis: evaluation of the influences of Foxp3 gene polymorphsism and treatment program. J Mol Neurosci, 2015; 55:891-897.
  • 28. Efekharian MM, Sayad A, Omrani MD, Ghannad MS, Noroozi R, Mazdeh M, et al. Single nucleotide polymorphisms in the Foxp3 gene are associated with incrased risk of relapsing-remitting multiple sclerosis. Hum Antibodies, 2016; doi: 10.3233/HAB-160299.
  • 29. Gholami M, Darvish H, Ahmadi H, Rahimi-Aliabadi S, Emamalizadeh B, Eslami Amirabadi MR, et al. Functional genetic variants of Foxp3 and risk of multiple sclerosis. Iran Red Crescent Med J, 2016; e34597.
There are 29 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Medical Science Research Articles
Authors

Nilgun Cekin

Ergun Pinarbasi

Aslihan Esra Bildirici

Seyda Akin

Ozlem Kayim Yildiz

Publication Date September 30, 2018
Acceptance Date July 4, 2018
Published in Issue Year 2018 Volume: 40 Issue: 3

Cite

AMA Cekin N, Pinarbasi E, Bildirici AE, Akin S, Kayim Yildiz O. Association between Multiple Sclerosis and FOXP3 Gene Promoter Region Mutations. CMJ. September 2018;40(3):226-232. doi:10.7197/223.vi.419261

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