title: Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis.
abstract: OBJECTIVE
  IL2RA/CD25, the gene for interleukin-2 receptor alpha, is emerging as a general susceptibility gene for autoimmune diseases because of its role in the development and function of regulatory T cells and the association of single-nucleotide polymorphisms (SNPs) within this gene with type 1 diabetes mellitus (DM), Graves' disease, rheumatoid arthritis (RA), and multiple sclerosis (MS). The aim of this study was to determine whether SNPs within the IL2RA/CD25 gene are associated with juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Three SNPs within the IL2RA/CD25 gene, that previously showed evidence of an association with either RA, MS, or type 1 DM, were selected for genotyping in UK JIA cases (n=654) and controls (n=3,849). Data for 1 SNP (rs2104286) were also available from North American JIA cases (n=747) and controls (n=1,161). Association analyses were performed using Plink software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.
  
  
  RESULTS
  SNP rs2104286 within the IL2RA/CD25 gene was significantly associated with UK JIA cases (OR for the allele 0.76 [95% CI 0.66-0.88], P for trend=0.0002). A second SNP (rs41295061) also showed modest evidence for association with JIA (OR 0.80 [95% CI 0.63-1.0], P=0.05). Association with rs2104286 was convincingly replicated in the North American JIA cohort (OR 0.84 [95% CI 0.65-0.99], P for trend=0.05). Meta-analysis of the 2 cohorts yielded highly significant evidence of association with JIA (OR 0.76 [95% CI 0.62-0.88], P=4.9x10(-5)).
  
  
  CONCLUSIONS
  These results provide strong evidence that the IL2RA/CD25 gene represents a JIA susceptibility locus. Further investigation of the gene using both genetic and functional approaches is now required.
authors.affiliation: University of Manchester, Manchester, UK. Anne.Hinks@manchester.ac.uk
authors.forename: Anne
authors.initials: A
authors.lastname: Hinks
authors.forename: Xiayi
authors.initials: X
authors.lastname: Ke
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Steve
authors.initials: S
authors.lastname: Eyre
authors.forename: John
authors.initials: J
authors.lastname: Bowes
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Susan D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: David N
authors.initials: DN
authors.lastname: Glass
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
mesh_terms: D001171:Arthritis, Juvenile / Q000235:genetics*; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D009656:North America; D020641:Polymorphism, Single Nucleotide; D012042:Registries; D006113:United Kingdom
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit