Association of human leukocyte antigen-DRB haplotype in multiple sclerosis population of Khuzestan, Iran

  • Nooshin Delfan Department of Genetics, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  • Hamid Galehdari Department of Genetics, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  • Mohammad Shafiei Department of Genetics, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  • Farideh Ghanbari-Mardasi Department of Genetics, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  • Tahereh Latifi Department of Genetics, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  • Nastaran Majdinasab Multiple Sclerosis Society, School of Rehabilitation, Ahvaz Jondishapour University of Medical Sciences, Ahvaz, Iran
  • Tahereh Seifi Department of Genetics, School of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Keywords: Multiple Sclerosis, Human Leukocyte Antigen-DRB5, Human Leukocyte Antigen-DRB1*1501, Polymerase Chain Reaction, Iran

Abstract

Background: One of the demyelinating and inflammatory diseases of the central nervous system (CNS) is multiple sclerosis (MS). Though pathogenesis of MS is still unknown, both genetic and environmental factors are involved. The human leukocyte antigen (HLA) class-II alleles including HLA-DRB5*01, DQB1*0602, DRB1*1501, and DQA1*0102 may have remarkable effect in MS risk although it is controversial in studies. As there is no data with respect to the HLA-DRB1*1501-DRB5*01 correlation with MS in Khuzestan Province, Iran, the goal of the survey was to investigate the association of this haplotype with MS in this population.

Methods: The study focused on DRB5*01-DRB1*1501 haplotype association with MS in 200 patients and 200 healthy individuals. Typing of HLA was carried out by polymerase chain reaction (PCR) amplification with sequence-specific primers (SSP) method. SPSS software was used for the statistical analyses.

Results: No association between DRB5*01+-DRB1*1501+ and MS was found (P = 0.156). Distribution of DRB1*1501+-DRB5*01- (carrying DRB1*1501+ but not DRB5*01-) and DRB1*1501--DRB5*01- haplotypes was statistically different between patients and controls (29.73% vs. 11.81%, P < 0.001) and (42.16% vs. 68.50%, P < 0.001), respectively. However, DRB1*1501--DRB5*01+ revealed no association with MS (15.13% vs. 11.81%, P = 0.403). HLA-DRB1*1501--DRB5*01+ was significantly more frequent among female patients with MS (16.19% vs. 6.12%, P = 0.019) and Persian group (17.11% vs. 5.79%, P = 0.027). Positive correlation of HLA-DRB1*1501+-DRB5*01- haplotype with the expanded disability status scale (EDSS) steps from 5 to 10 was observed (62.50% vs. 25.76%, P = 0.026). Moreover, no meaningful association was shown among the haplotypes with EDSS, course of MS, ethnicity, and gender.

Conclusion: Our findings suggest that DRB1*1501+-DRB5*01- and DRB1*1501--DRB5*01- haplotypes may have positive association with MS risk. Also, this survey indicates that HLA-DRB1*1501--DRB5*01+ is involved in susceptibility of the disease among women and Persians. DRB1*1501+-DRB5*01- genotype frequency may have a key role in MS developing.

References

1. Galehdari H, Zabihi R, Ghanbari Mardasi F, Delfan N, Rahim F. Association of IL-10 (-1082 G/A Polymorphism) with multiple sclerosis risk: A systematic review and meta-analysis. Asian Journal of Cell Biology 2015; 10(2): 25-34.
2. Delfan N, Galehdari H, Kazeminejad SR, Shafiei M, Zabihi R, Majdinasab N. Analysis of HLA-DRB1*1501 in multiple sclerosis patients in Khuzestan Province, Iran. Zahedan J Res Med Sci 2017; 19(3): e5647.
3. Prat E, Tomaru U, Sabater L, Park DC. HLA-DRB5*0101 and-DRB1*1501 expression in the multiple sclerosis-associated HLA-DR15 haplotype. J Neuroimmunol 2005; 167(1-2): 108-19.
4. Quandt JA, Huh J, Baig M, Yao K, Ito N, Bryant M, et al. Myelin basic protein-specific TCR/HLA-DRB5*01: 01 transgenic mice support the etiologic role of DRB5*01:01 in multiple sclerosis. J Immunol 2012; 189(6): 2897-908.
5. Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, et al. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 2002; 3(10): 940-3.
6. Gregersen JW, Kranc KR, Ke X, Svendsen P, Madsen LS, Thomsen AR, et al. Functional epistasis on a common MHC haplotype associated with multiple sclerosis. Nature 2006; 443(7111): 574-7.
7. Krogsgaard M, Wucherpfennig KW, Cannella B, Hansen BE, Svejgaard A, Pyrdol J, et al. Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex. J Exp Med 2000; 191(8): 1395-412.
8. Kollaee A, Ghaffarpor M, Ghlichnia HA, Ghaffari SH, Zamani M. The influence of the HLA-DRB1 and HLA-DQB1 allele heterogeneity on disease risk and severity in Iranian patients with multiple sclerosis. Int J Immunogenet 2012; 39(5): 414-22.
9. Amirzargar AA, Tabasi A, Khosravi F, Kheradvar A, Rezaei N, Naroueynejad M, et al. Optic neuritis, multiple sclerosis and human leukocyte antigen: Results of a 4-year follow-up study. Eur J Neurol 2005; 12(1): 25-30.
10. Shahbazi M, Roshandel D, Ebadi H, Fathi D, Zamani M, Boghaee M, et al. High frequency of the IL-2 -330 T/HLA-DRB1*1501 haplotype in patients with multiple sclerosis. Clin Immunol 2010; 137(1): 134-8.
11. Sayad A. The association of -330 interleukin-2 gene polymorphism and HLA-DR15 allele in Iranian patients with multiple sclerosis. Int J Immunogenet 2014; 41(4): 330-4.
12. Hamid M, Bokharaei Merci H, Galehdari H, Saberi AH, Kaikhaei B, Mohammadi-Anaei M, et al. A novel alpha-thalassemia nonsense mutation in HBA2: C.382 A > T globin gene. Arch Iran Med 2014; 17(7): 475-6.
13. Galehdari H, Salehi B, Azmoun S, Keikhaei B, Zandian KM, Pedram M. Comprehensive spectrum of the beta-Thalassemia mutations in Khuzestan, southwest Iran. Hemoglobin 2010; 34(5): 461-8.
14. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology 1983; 33(11): 1444-52.
15. Latifi Pakdehi T, Shafiei M, Galehdari H. HLA DRB5*01 association survey with multiple sclerosis in Khuzestan province of Iran. Zahedan J Res Med Sci 2019; 19(8): e9186.
16. Fogdell A, Hillert J, Sachs C, Olerup O. The multiple sclerosis-and narcolepsy-associated HLA class II haplotype includes the DRB5*0101 allele. Tissue Antigens 1995; 46(4): 333-6.
17. Caillier SJ, Briggs F, Cree BA, Baranzini SE, Fernandez-Vina M, Ramsay PP, et al. Uncoupling the roles of HLA-DRB1 and HLA-DRB5 genes in multiple sclerosis. J Immunol 2008; 181(8): 5473-80.
18. Brum DG, Barreira AA, dos Santos AC, Kaimen-Maciel DR, Matiello M, Costa RM, et al. HLA-DRB association in neuromyelitis optica is different from that observed in multiple sclerosis. Mult Scler 2010; 16(1): 21-9.
19. Fukazawa T, Kikuchi S, Sasaki H, Yabe I, Miyagishi R, Hamada T, et al. Genomic HLA profiles of MS in Hokkaido, Japan: Important role of DPB1*0501 allele. J Neurol 2000; 247(3): 175-8.
20. Kaimen-Maciel DR, Reiche EM, Borelli SD, Morimoto HK, Melo FC, Lopes J, et al. HLA-DRB1* allele-associated genetic susceptibility and protection against multiple sclerosis in Brazilian patients. Mol Med Rep 2009; 2(6): 993-8.
21. Kouri I, Papakonstantinou S, Bempes V, Vasiliadis HS, Kyritsis AP, Pelidou SH. HLA associations with multiple sclerosis in Greece. J Neurol Sci 2011; 308(1-2): 28-31.
22. Delfan N, Galehdari H, Shafiei M, Khatami SR. Distribution analysis of HLA-DRB1*1501, -DQA1*0102, -DQB1*0602, -DRB5*01, -A*0301 alleles and haplotypes in normal population of Khuzestan Province. Focus Sci 2017; 3(3): 1-6.
23. Oksenberg JR, Barcellos LF, Cree BA, Baranzini SE, Bugawan TL, Khan O, et al. Mapping multiple sclerosis susceptibility to the HLA-DR locus in African Americans. Am J Hum Genet 2004; 74(1): 160-7.
24. Etzensperger R, McMahon RM, Jones EY, Fugger L. Dissection of the multiple sclerosis associated DR2 haplotype. J Autoimmun 2008; 31(3): 201-7.
25. Fogdell-Hahn A, Ligers A, Gronning M, Hillert J, Olerup O. Multiple sclerosis: A modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. Tissue Antigens 2000; 55(2): 140-8.
26. Harbo HF, Lie BA, Sawcer S, Celius EG, Dai KZ, Oturai A, et al. Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis. Tissue Antigens 2004; 63(3): 237-47.
Published
2018-05-28
How to Cite
1.
Delfan N, Galehdari H, Shafiei M, Ghanbari-Mardasi F, Latifi T, Majdinasab N, Seifi T. Association of human leukocyte antigen-DRB haplotype in multiple sclerosis population of Khuzestan, Iran. Iran J Neurol. 17(4):154-160.
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Original Article(s)