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Asouri M, Alinejad Rokni H, Sahraian M A, Fattahi S, Motamed N, Doosti R, et al . Analysis of Single Nucleotide Polymorphisms in HLA-DRA, IL2RA, and HMGB1 Genes in Multiple Sclerosis. rbmb.net 2020; 9 (2) :199-208
URL: http://rbmb.net/article-1-459-en.html
Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
Abstract:   (3350 Views)
Background: Multiple sclerosis (MS) is a common demyelinating neurodegenerative disorder with significant heritability. Previous studies have associated genetic variants in human leukocyte antigen (HLA) complex, IL2RA, and HMGB1 genes with the pathophysiology of MS.

Methods: In order to investigate the gene association in the Iranian population, we performed a genotyping study of 36 variants in the mentioned genes using Sanger sequencing in 102 MS patients and 113 healthy controls.

Results: Our results identified significant associations as well as significant allele frequency differences in some of the studied single-nucleotide polymorphisms including rs4935356, rs3177928, and rs7197 from HLA-DRA gene, and rs12722489 and rs12722490 variants from IL2RA gene (p< 0.05). Moreover, the strong linkage disequilibrium of two common haplotypes was estimated from the HLA-DRA gene.

Conclusions: This association study may suggest the role of these polymorphisms in the genetic susceptibility of MS in the Iranian population and would facilitate the recognition of causative variants in this disease.
Full-Text [PDF 301 kb]   (1585 Downloads)    
Type of Article: Original Article | Subject: Molecular Biology
Received: 2020/02/3 | Accepted: 2020/02/23 | Published: 2020/10/7

References
1. Martin R, Sospedra M, Rosito M, Engelhardt B. Current multiple sclerosis treatments have improved our understanding of MS autoimmune pathogenesis. Eur J Immunol. 2016;46(9):2078-90. [DOI:10.1002/eji.201646485] [PMID]
2. Jamali M, Rostami Rad M, Anani Sarab G, Mahdavi R. IL-33 polymorphism rs1929992 and its association with susceptibility to different pattern of multiple sclerosis. Tehran Univers Med J. 2018;76(7):446-451.
3. Klaren RE, Sasaki JE, McAuley E, Motl RW, Health. Patterns and predictors of change in moderate-to-vigorous physical activity over time in multiple sclerosis. J Phys Act Health. 2017;14(3):183-188. [DOI:10.1123/jpah.2016-0335] [PMID]
4. Csepany T. Diagnosis of multiple sclerosis: A review of the 2017 revisions of the McDonald criteria. Ideggyogyaszati szemle. 2018;71(9-10):321-329. [DOI:10.18071/isz.71.0321] [PMID]
5. Pan Y, Wang K-S, Wang L, Wu L-Y. Common Variants in HLA-DRA Gene are Associated with Alcohol Dependence in Two Caucasian Samples. J Mol Neurosci. 2013;49(3):574-81. [DOI:10.1007/s12031-012-9869-3] [PMID]
6. Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nat Rev Neurol. 2017;13(1):25-36. [DOI:10.1038/nrneurol.2016.187] [PMID]
7. Berge T, Leikfoss I, Brorson I, Bos S, Page C, Gustavsen M, et al. The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells. Genes Immun. 2016;17(2):118-27. [DOI:10.1038/gene.2015.61] [PMID] [PMCID]
8. Fang P, Schachner M, Shen Y-Q. HMGB1 in development and diseases of the central nervous system. Mol Neurobiol. 2012;45(3):499-506. [DOI:10.1007/s12035-012-8264-y] [PMID]
9. Malhotra S, Fissolo N, Tintoré M, Wing AC, Castillo J, Vidal-Jordana A, et al. Role of high mobility group box protein 1 (HMGB1) in peripheral blood from patients with multiple sclerosis. J Neuroinflammation. 2015;12:48. [DOI:10.1186/s12974-015-0269-9] [PMID] [PMCID]
10. Zhen C, Wang Y, Li D, Zhang W, Zhang H, Yu X, et al. Relationship of High-mobility group box 1 levels and multiple sclerosis: A systematic review and meta-analysis. Mult Scler Rel Disord. 2019;31:87-92. [DOI:10.1016/j.msard.2019.03.030] [PMID]
11. Andersson Å, Covacu R, Sunnemark D, Danilov AI, Dal Bianco A, Khademi M, et al. Pivotal advance: HMGB1 expression in active lesions of human and experimental multiple sclerosis. J Leukoc Biol. 2008;84(5):1248-55. [DOI:10.1189/jlb.1207844] [PMID]
12. Buhelt S, Søndergaard HB, Oturai A, Ullum H, von Essen MR, Sellebjerg F. Relationship between Multiple Sclerosis-Associated IL2RA Risk Allele Variants and Circulating T Cell Phenotypes in Healthy Genotype-Selected Controls. Cells. 2019;8(6):634. [DOI:10.3390/cells8060634] [PMID] [PMCID]
13. Wang S, Zhai H, Su Y, Wang Y. IL-17F but not IL-17A gene polymorphism confers risk to multiple sclerosis in a Chinese Han population. Journal of the Neurological Sciences. 2014;342(1-2):133-136. [DOI:10.1016/j.jns.2014.05.004] [PMID]
14. Wolin A, Lahtela EL, Anttila V, Petrek M, Grunewald J, van Moorsel CH, et al. snP Variants in Major histocompatibility complex are associated with sarcoidosis susceptibility-a Joint analysis in Four european Populations. Front Immunol. 2017;8:422. [DOI:10.3389/fimmu.2017.00422] [PMID] [PMCID]
15. Mentzer AJ, Brenner N, Allen N, Littlejohns TJ, Chong AY, Cortes A, et al. Identification of host-pathogen-disease relationships using a scalable Multiplex Serology platform in UK Biobank. medRxiv. 2019:19004960. [DOI:10.1101/19004960]
16. Mahmud SA, Manlove LS, Farrar MA. Interleukin-2 and STAT5 in regulatory T cell development and function. JAKSTAT. 2013;2(1):e23154. [DOI:10.4161/jkst.23154] [PMID] [PMCID]
17. Afanasyeva MA, Putlyaeva LV, Demin DE, Kulakovskiy IV, Vorontsov IE, Fridman MV, et al. The single nucleotide variant rs12722489 determines differential estrogen receptor binding and enhancer properties of an IL2RA intronic region. PLoS One. 2017;12(2):e0172681. [DOI:10.1371/journal.pone.0172681] [PMID] [PMCID]
18. Cavanillas ML, Alcina A, Núñez C, De Las Heras V, Fernández-Arquero M, Bartolomé M, et al. Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk. European Journal of Human Genetics. 2010;18(7):794-799. [DOI:10.1038/ejhg.2010.15] [PMID] [PMCID]
19. Erlandsson Harris H, Andersson U. Mini‐review: the nuclear protein HMGB1 as a proinflammatory mediator. Eur J Immunol. 2004;34(6):1503-12. [DOI:10.1002/eji.200424916] [PMID]
20. Friggeri A, Yang Y, Banerjee S, Park Y-J, Liu G, Abraham E. HMGB1 inhibits macrophage activity in efferocytosis through binding to the αvβ3-integrin. Am J Physiol Cell Physiol. 2010;299(6):C1267-C1276. [DOI:10.1152/ajpcell.00152.2010] [PMID] [PMCID]
21. Ek M, Popovic K, Erlandsson Harris H, Söderberg Nauclér C, Wahren‐Herlenius M. Increased extracellular levels of the novel proinflammatory cytokine high mobility group box chromosomal protein 1 in minor salivary glands of patients with Sjögren's syndrome. Arthritis Rheum. 2006;54(7):2289-94. [DOI:10.1002/art.21969] [PMID]

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