Association between Multiple Sclerosis and FOXP3 Gene Promoter Region Mutations

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

doi:10.7197/223.vi.419261

EN

Association between Multiple Sclerosis and FOXP3 Gene Promoter Region Mutations

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

Kaynakça

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.

Ayrıntılar

Birincil Dil

İngilizce

Konular

Sağlık Kurumları Yönetimi

Bölüm

Araştırma Makalesi

Yazarlar

Nilgun Cekin
Türkiye

Ergun Pinarbasi ^*
Türkiye

Aslihan Esra Bildirici
Türkiye

Seyda Akin
Türkiye

Ozlem Kayim Yildiz
Türkiye

Yayımlanma Tarihi

30 Eylül 2018

Gönderilme Tarihi

27 Nisan 2018

Kabul Tarihi

4 Temmuz 2018

Yayımlandığı Sayı

Yıl 2018 Cilt: 40 Sayı: 3

DOI

https://doi.org/10.7197/223.vi.419261

IZ

https://izlik.org/JA48HG49GT

Kaynak Göster

RIS / Bibtex

AMA

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

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Medical Hypotheses

https://doi.org/10.1016/j.mehy.2024.111382

Association between Multiple Sclerosis and FOXP3 Gene Promoter Region Mutations

Abstract

Keywords

Öz

Kaynakça

Ayrıntılar

Birincil Dil

Konular

Bölüm

Yazarlar

Yayımlanma Tarihi

Gönderilme Tarihi

Kabul Tarihi

Yayımlandığı Sayı

DOI

IZ

Kaynak Göster

Cited By

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