Connection of the IL2RA/CD25 gene with juvenile idiopathic arthritis.
Hinks A, Ke X, Barton A, Eyre S, Bowes J, Worthington J, Thompson SD, Langefeld CD, Glass DN, Thomson W; UK Rheumatoid Arthritis Genetics Consortium; British Society of Paediatric and Adolescent Rheumatology Study Group.
Collaborators (32)
Wilson AG, Morgan A, Emery P, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Symmons D, Abinum M, Becker M, Bell A, Craft A, Crawley E, David J, Foster H, Gardener-Medwin J, Griffin J, Hall A, Hall M, Herrick A, Hollingworth P, Holt L, Jones S, Pountain G, Ryder C, Southwood T, Stewart I, Venning H, Wedderburn L, Woo P, Wyatt S.
University of Manchester, Manchester, UK.
Anne.Hinks@manchester.ac.uk
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 *** 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 *** with juvenile idiopathic arthritis (JIA). METHODS: Three SNPs within the IL2RA/CD25 gene, that previously showed evidence of an *** 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). *** 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 *** 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 *** with JIA (OR 0.80 [95% CI 0.63-1.0], P=0.05). *** 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 *** 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.