Document Type : Original Article


1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran


Background: Multiple sclerosis (MS) is a complex incurable neurodegenerative disease featuring demyelination of neurons, resulting in impairment of neuron impulses. Recently, an association of two single nucleotide polymorphisms (SNP) (rs2104286 and rs12722489) in interleukin 2 receptor subunit alpha (IL2RA) gene was found to be a risk factor of MS in white European population. Therefore, we performed a study to investigate the contribution of these two intronic variations in Iranian patients with MS.
Methods: We determined the genotypes of rs2104286 and rs12722489 in patients with MS (n = 100) and in the control group (n = 111). The SNPs were genotyped using tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) for both of SNPs. Statistical analysis was performed by SPSS software. Also, odds ratios (ORs) and 95% confidence interval (CI) were calculated.
Results: Logistic regression revealed that various genotypes of rs12722489, regarding sex-adjusted effect, yielded meaningful association with MS risk in Iranian patients (OR = 2.67, 95% CI: 1.03-6.90). However, no association was obtained for rs2104286 and rs12722489 with MS.
Conclusion: The results confirmed partially the reports in white European population performed recently. However, further investigation in larger scale is necessary to validate our study.


  1. Gholami M, Darvish H, Ahmadi H, Rahimi Aliabadi S, Emamalizadeh B, Eslami Eslami Amirabadi MR, et al. Functional genetic variants of FOXP3 and risk of multiple sclerosis. Iran Red Crescent Med J 2017; 19(1): e34597.
  2. Pugliatti M, Rosati G, Carton H, Riise T, Drulovic J, Vecsei L, et al. The epidemiology of multiple sclerosis in Europe. Eur J Neurol 2006; 13(7): 700-22.
  3. Ascherio A, Munger KL. Environmental risk factors for multiple sclerosis. Part I: The role of infection. Ann Neurol 2007; 61(4): 288-99.
  4. Gilden DH. Infectious causes of multiple sclerosis. Lancet Neurol 2005; 4(3): 195-202.
  5. Trapp BD, Nave KA. Multiple sclerosis: An immune or neurodegenerative disorder? Annu Rev Neurosci 2008; 31: 247-69.
  6. Barcellos LF, Sawcer S, Ramsay PP, Baranzini SE, Thomson G, Briggs F, et al. Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Hum Mol Genet 2006; 15(18): 2813-24.
  7. Gourraud PA, Harbo HF, Hauser SL, Baranzini SE. The genetics of multiple sclerosis: An up-to-date review. Immunol Rev 2012; 248(1): 87-103.
  8. Kantarci OH, Hebrink DD, Achenbach SJ, Atkinson EJ, Waliszewska A, Buckle G, et al. CTLA4 is associated with susceptibility to multiple sclerosis. J Neuroimmunol 2003; 134(1-2): 133-41.
  9. Huizinga TW, Westendorp RG, Bollen EL, Keijsers V, Brinkman BM, Langermans JA, et al. TNF-alpha promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients. J Neuroimmunol 1997; 72(2): 149-53.
  10. Ramagopalan SV, Dyment DA, Cader MZ, Morrison KM, Disanto G, Morahan JM, et al. Rare variants in the CYP27B1 gene are associated with multiple sclerosis. Ann Neurol 2011; 70(6): 881-6.
  11. Weber F, Fontaine B, Cournu-Rebeix I, Kroner A, Knop M, Lutz S, et al. IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations. Genes Immun 2008; 9(3): 259-63.
  12. Fontenot JD, Rasmussen JP, Gavin MA, Rudensky AY. A function for interleukin 2 in Foxp3-expressing regulatory T cells. Nat Immunol 2005; 6(11): 1142-51.
  13. Hinks A, Ke X, Barton A, Eyre S, Bowes J, Worthington J, et al. Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis Rheum 2009; 60(1): 251-7.
  14. Alcina A, Fedetz M, Ndagire D, Fernandez O, Leyva L, Guerrero M, et al. IL2RA/CD25 gene polymorphisms: Uneven association with multiple sclerosis (MS) and type 1 diabetes (T1D). PLoS One 2009; 4(1): e4137.
  15. Lowe CE, Cooper JD, Brusko T, Walker NM, Smyth DJ, Bailey R, et al. Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet 2007; 39(9): 1074-82.
  16. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16(3): 1215.
  17. Alsahebfosoul F, Salehi R, Ghaffari S, Jahanbani-Ardakani H, Etemadifar M, Kazemi M, et al. CD25 gene polymorphism and multiple sclerosis. Mult Scler Relat Disord 2017; 18: 117-8.
  18. Hassan-Smith G, Douglas MR. Epidemiology and diagnosis of multiple sclerosis. Br J Hosp Med (Lond) 2011; 72(10): M146-M151.