This meta-analysis studied the association between interleukin 2 receptor a (IL2RA) gene polymorphisms rs2104286 and rs12722489 and susceptibility to multiple sclerosis (MS). Case-control genetic association studies published before January 2011 were retrieved from the PubMed and EMBASE databases and the Cochrane Library. Eight studies comprising 13 569 patients and 23 435 controls met the selection criteria for meta-analysis of the IL2RA rs2104286 polymorphism. Using a fixed-effects model, the T allele and the TT and TT + TC genotypes of the IL2RA rs2104286 polymorphism were found to be associated with MS. Five studies comprising 5643 patients and 6415 controls met the selection criteria for meta-analysis of the IL2RA rs12722489 polymorphism. Using a fixed-effects model, the C allele and the CC genotype of the IL2RA rs12722489 polymorphism were found to be associated with MS but the CC + CT genotype was not. It was concluded that both of the IL2RA gene polymorphisms, rs2104286 and rs12722489, were associated with increased susceptibility to MS.
BaranziniSEWangJGibsonRA: Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis. Hum Mol Genet2009; 18: 767–778.
5.
EbersGC: Environmental factors and multiple sclerosis. Lancet Neurol2008; 7: 268–277.
6.
DymentDAEbersGCSadovnickAD: Genetics of multiple sclerosis. Lancet Neurol2004; 3: 104–110.
7.
DeLucaGCRamagopalanSVHerreraBM: An extremes of outcome strategy provides evidence that multiple sclerosis severity is determined by alleles at the HLA-DRB1 locus. Proc Natl Acad Sci U S A2007; 52: 20896–20901.
8.
HainesJLTerwedowHABurgessK: Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group. Hum Mol Genet1998; 7: 1229–1234.
9.
HaflerDACompstonASawcerS: Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med2007; 357: 851–862.
10.
Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene): Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20. Nat Genet2009; 41: 824–828.
11.
RubioJPStankovichJFieldJ: Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes Immun2008; 9: 624–630.
12.
CavanillasMLAlcinaANúñezC: Polymorphisms in the IL2, IL2RA and IL2RB genes in multiple sclerosis risk. Eur J Hum Genet2010; 18: 794–799.
13.
AlcinaAFedetzMNdagireD: IL2RA/CD25 gene polymorphisms: uneven association with multiple sclerosis (MS) and type 1 diabetes (T1D). PLoS One2009; 4: e4137.
14.
PereraDStankovichJButzkuevenH: Fine mapping of multiple sclerosis susceptibility genes provides evidence of allelic heterogeneity at the IL2RA locus. J Neuroimmunol2009; 211: 105–109.
15.
MaierLMLoweCECooperJ: IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet2009; 5: e1000322.
16.
AkkadDAHoffjanSParwezE Petrasch: Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients. J Autoimmun2009; 32: 110–115.
17.
HoppenbrouwersIAAulchenkoYSJanssensAC: Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis. J Hum Genet2009; 54: 676–680.
18.
WeberFFontaineBRebeixI Cournu: IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations. Genes Immun2008; 9: 259–263.
19.
HandollHH: Systematic reviews on rehabilitation interventions. Arch Phys Med Rehabil2006; 87: 875.
20.
Huedo-MedinaTBSánchez-MecaJMarín-MartínezF: Assessing heterogeneity in meta-analysis: Q statistic or I2 index?Psychol Methods2006; 11: 193–206.
21.
DerSimonianRLairdN: Meta-analysis in clinical trials. Controlled Clin Trials1986; 7: 177–188.
22.
EggerMSmithG DaveySchneiderM: Bias in meta-analysis detected by a simple, graphical test. BMJ1997; 315: 629–634.
SchmidtHWilliamsonDAshley-KochA: HLA-DR15 haplotype and multiple sclerosis: A HuGE review. Am J Epidemiol2007; 165: 1097–1109.
25.
BarcellosLFSawcerSRamsayPP: Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis. Hum Mol Genet2006; 15: 2813–2824.
26.
StankovichJButzkuevenHMarriottM: HLA-DRB1 associations with disease susceptibility and clinical course in Australians with multiple sclerosis. Tissue Antigens2009; 74: 17–21.
27.
DeanGYeoTWGorisA: HLA-DRB1 and multiple sclerosis in Malta. Neurology2008; 70: 101–105.
28.
McElroyJPOksenbergJR: Multiple sclerosis genetics. Curr Top Microbiol Immunol2008; 318: 45–72.
29.
SvejgaardA: The immunogenetics of multiple sclerosis. Immunogenetics2008; 60: 275–286.
30.
BahreiniSAJabalameliMRSaadatniaM: The role of non-HLA single nucleotide polymorphisms in multiple sclerosis susceptibility. J Neuroimmunol2010; 229: 5–15.
31.
RamagopalanSVAndersonCSadovnickAD: Genome-wide study of multiple sclerosis. N Engl J Med2007; 357: 2199–2201.
32.
RubinLAGalliFGreeneWC: The molecular basis for the generation of the human soluble interleukin 2 receptor. Cytokine1990; 2: 330–336.
33.
RobbRJKutnyRM: Structure-function relationships for the IL 2-receptor system. IV: Analysis of the sequence and ligand-binding properties of soluble Tac protein. J Immunol1987; 139: 855–862.
34.
KimHPImbertJLeonardWJ: Both integrated and differential regulation of components of the IL-2/IL-2 receptor system. Cytokine Growth Factor Rev2006; 17: 349–366.
35.
LoweCECooperJDBruskoT: Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes. Nat Genet2007; 39: 1074–1082.
36.
BrandOJLoweCEHewardJM: Association of the interleukin-2 receptor alpha (IL-2Rα)/CD25 gene region with Graves’ disease using a multilocus test and tag SNPs. Clin Endocrinol (Oxf)2007; 66: 508–512.
37.
LindseyJW: Familiar recurrence rates and genetic models of multiple sclerosis. Am J Med Genet A2005; 135: 53–58.
38.
WasayMKhatriIAKhealaniB: MS in Asian countries. Int MS J2006; 13: 58–65.
