Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

UK Rheumatoid Arthritis Genetics Consortium, British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group

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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)). CONCLUSION: 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.
Original languageEnglish
Pages (from-to)251-257
Number of pages7
JournalArthritis & Rheumatism
Volume60
Issue number1
Early online date30 Dec 2008
DOIs
Publication statusPublished - Jan 2009

Keywords

  • arthritis, juvenile rheumatoid
  • cohort studies
  • gene frequency
  • genetic predisposition to disease
  • genotype
  • Great Britain
  • humans
  • interleukin-2 receptor alpha subunit
  • North America
  • polymorphism, single nucleotide
  • registries

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    UK Rheumatoid Arthritis Genetics Consortium, & British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group (2009). Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis. Arthritis & Rheumatism, 60(1), 251-257. https://doi.org/10.1002/art.24187