Volume 33, Issue 2 (May 2022)                   Studies in Medical Sciences 2022, 33(2): 88-99 | Back to browse issues page

Ethics code: IR.UMSU.REC.1397.131


XML Persian Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Akbariazar E, Angaji A, Pakzad P, Abdi Rad I, Musarrezaii Aghdam A. STUDY OF ASSOCIATION BETWEEN SUSCEPTIBLE VARIANTS IN GENES WITH VITAMIN D RESPONSE ELEMENTS AND THE RISK OF RELAPSING-REMITTING MULTIPLE-SCLEROSIS IN IRANIAN AZERI POPULATION. Studies in Medical Sciences 2022; 33 (2) :88-99
URL: http://umj.umsu.ac.ir/article-1-5736-en.html
Department of Cell and Molecular Biology, Faculty of biological sciences, Kharazmi University, Tehran, Iran , angaji@khu.ac.ir
Abstract:   (1226 Views)
Background & Aims: Multiple sclerosis (MS) (MIM #126200) is a chronic, inflammatory, demyelinating disorder of the central nervous system (CNS) that is the most common reason for non-traumatic neurological defects among young people. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in genes with vitamin D response elements (VDREs) in their regulatory regions and the risk of relapsing-remitting multiple sclerosis (RR-MS) in the Iranian Azeri population.
Materials & Methods: A total of 129RR-MS cases and 200 normal controls from West Azerbaijan were recruited in this study. We genotyped the fourteen MS susceptible variants in genes with vitamin D response elements that emerged from previous genome-wide association studies (GWAS), using Tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) assay in every participant. Chi-square, Fisher's exact test, and allelic and genotypic regression analysis were used to investigate the association of these polymorphisms with RRMS.
Results: Three polymorphisms showed significant association (p-value < 0.05) with RR-MS. In particular, rs4410871 of PVT1 (p-value= 0.035, TT vs CC OR[95%CI]= 2.775 (1.253-6.146)), rs212405 of TAGAP (p-value=0.016, AA vs TT OR[95%CI]= 2.463 (1.255-4.835)), and rs7090512 of IL2RA (p-value= 0.008, CC vs TT  OR[95%CI]= 2.865 (1.433-5.731) ) were identified as susceptible risk factors in our group. 
Conclusion: The current study replicated fourteen susceptible variants in genes with vitamin D response elements and the risk of RR-MS in the Iranian Azeri population, which implies the existence of some similarities between the MS genetic structure of the GWAS populations and the studied Iranian Azeri population.
Full-Text [PDF 292 kb]   (412 Downloads)    
Type of Study: Research | Subject: ژنتیک

References
1. Fauci AS. Harrison's principles of internal medicine: McGraw-Hill Education; 2015. [URL]
2. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler 2020;26(14):1816-21. [DOI:10.1177/1352458520970841] [PMID] [PMCID]
3. Goldenberg MM. Multiple sclerosis review. Pharm Ther 2012;37(3):175-84. [PMID]
4. Trapp BD, Nave KA. Multiple sclerosis: an immune or neurodegenerative disorder? Annu Rev Neurosci 2008;31(1):247-69. [DOI:10.1146/annurev.neuro.30.051606.094313] [PMID]
5. Bitsch A, Brück W. Differentiation of multiple sclerosis subtypes: implications for treatment. CNS Drugs 2002;16(6):405-18. [DOI:10.2165/00023210-200216060-00004] [PMID]
6. Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. Harrison's principles of internal medicine, 19e: Mcgraw-hill; 2015. [URL]
7. Dyment DA, Sadovnick AD, Ebers GC. Genetics of multiple sclerosis. Hum Mol Genet 1997;6(10):1693-8. [DOI:10.1093/hmg/6.10.1693] [PMID]
8. Compston A, Coles A. Multiple sclerosis. Lancet 2008;372(9648):1502-17. [DOI:10.1016/S0140-6736(08)61620-7] [PMID]
9. Hollenbach JA, Oksenberg JR. The immunogenetics of multiple sclerosis: A comprehensive review. J Autoimmun 2015;64:13-25. [DOI:10.1016/j.jaut.2015.06.010] [PMID] [PMCID]
10. Sawcer S, Hellenthal G, Pirinen M, Spencer CCA, Patsopoulos NA, Moutsianas L, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011;476(7359):214-9. [DOI:10.1038/nature10251] [PMID] [PMCID]
11. Ramagopalan SV, Maugeri NJ, Handunnetthi L, Lincoln MR, Orton SM, Dyment DA, et al. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet 2009;5(2):e1000369. [DOI:10.1371/journal.pgen.1000369] [PMID] [PMCID]
12. Lu M, McComish BJ, Burdon KP, Taylor BV, Körner H. The Association Between Vitamin D and Multiple Sclerosis Risk: 1,25(OH)(2)D(3) Induces Super-Enhancers Bound by VDR. Front Immunol 2019;10:488. [DOI:10.3389/fimmu.2019.00488] [PMID] [PMCID]
13. Disanto G, Sandve GK, Berlanga-Taylor AJ, Ragnedda G, Morahan JM, Watson CT, et al. Vitamin D receptor binding, chromatin states and association with multiple sclerosis. Hum Mol Genet 2012;21(16):3575-86. [DOI:10.1093/hmg/dds189] [PMID] [PMCID]
14. Lassmann H. Multiple Sclerosis Pathology. Cold Spring Harb Perspect Med 2018;8(3):a028936. [DOI:10.1101/cshperspect.a028936] [PMID] [PMCID]
15. Huang WJ, Chen WW, Zhang X. Multiple sclerosis: Pathology, diagnosis and treatments (Review). Exp Ther Med 2017;13(6):3163-6. [DOI:10.3892/etm.2017.4410] [PMID] [PMCID]
16. Jersild C, Svejgaard A, Fog T. HL-A antigens and multiple sclerosis. Lancet 1972;1(7762):1240-1. [DOI:10.1016/S0140-6736(72)90962-2] [PMID]
17. Jersild C, Svejgaard A, Fog T, Ammitzboll T. HL-A antigens and diseases. I. Multiple sclerosis. Tissue Antigens 1973;3(4):243-50. [DOI:10.1111/j.1399-0039.1973.tb01002.x] [PMID]
18. Cotsapas C, Mitrovic M. Genome-wide association studies of multiple sclerosis. Clin Transl Immunol 2018;7(6):e1018-e. [] [PMID] [PMCID]
19. Altshuler D, Daly MJ, Lander ES. Genetic mapping in human disease. Science 2008;322(5903):881-8. [DOI:10.1126/science.1156409] [PMID] [PMCID]
20. Sintzel MB, Rametta M, Reder AT. Vitamin D and Multiple Sclerosis: A Comprehensive Review. Neurol Ther 2018;7(1):59-85. [] [PMID] [PMCID]
21. Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007;357(9):851-62. [DOI:10.1056/NEJMoa073493] [PMID]
22. Rubio JP, Stankovich J, Field J, Tubridy N, Marriott M, Chapman C, et al. Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes Immun 2008;9(7):624-30. [DOI:10.1038/gene.2008.59] [PMID]
23. 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. Eur J Hum Genet 2010;18(7):794-9. [] [PMID] [PMCID]
24. Perera D, Stankovich J, Butzkueven H, Taylor BV, Foote SJ, Kilpatrick TJ, et al. Fine mapping of multiple sclerosis susceptibility genes provides evidence of allelic heterogeneity at the IL2RA locus. J Neuroimmunol 2009;211(1):105-9. [DOI:10.1016/j.jneuroim.2009.03.010] [PMID]
25. Ainiding G, Kawano Y, Sato S, Isobe N, Matsushita T, Yoshimura S, et al. Interleukin 2 receptor α chain gene polymorphisms and risks of multiple sclerosis and neuromyelitis optica in southern Japanese. J Neurol Sci 2014;337(1-2):147-50. [DOI:10.1016/j.jns.2013.11.037] [PMID]
26. Chen R, Stahl EA, Kurreeman FAS, Gregersen PK, Siminovitch KA, Worthington J, et al. Fine mapping the TAGAP risk locus in rheumatoid arthritis. Genes Immun 2011;12(4):314-8. [] [PMID] [PMCID]
27. Arshad M, Bhatti A, John P, Jalil F, Borghese F, Kawalkowska JZ, et al. T cell activation Rho GTPase activating protein (TAGAP) is upregulated in clinical and experimental arthritis. Cytokine 2018;104:130-5. [DOI:10.1016/j.cyto.2017.10.002] [PMID]
28. Berge T, Leikfoss IS, Brorson IS, Bos SD, Page CM, Gustavsen MW, 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. [] [PMID] [PMCID]
29. International Multiple Sclerosis Genetics C, Beecham AH, Patsopoulos NA, Xifara DK, Davis MF, Kemppinen A, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet 2013;45(11):1353-60. [] [PMID] [PMCID]
30. Kozin MS, Kulakova OG, Favorova OO. Involvement of Mitochondria in Neurodegeneration in Multiple Sclerosis. Biochemistry Mosc 2018;83(7):813-30. [DOI:10.1134/S0006297918070052] [PMID]
31. Kiselev I, Kozin M, Baulina N, Pavlova GV, Boyko A, Kulakova O, et al. Polymorphic variants in the PVT1 locus affect multiple sclerosis severity. Neurology, neuropsychiatry, Psychosomatics 2020;12:4-8. [DOI:10.14412/2074-2711-2020-1S-4-8]
32. Kozin M, Kulakova O, Kiselev I, Baulina N, Boyko A, Favorova O. Mitonuclear interactions influence multiple sclerosis risk. Gene 2020;758:144962. [DOI:10.1016/j.gene.2020.144962] [PMID]

Add your comments about this article : Your username or Email:
CAPTCHA

Send email to the article author


Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Studies in Medical Sciences

Designed & Developed by : Yektaweb