Association of the IL2RA/CD25 gene with juvenile idiopathic arthritis

Anne Hinks, Xiayi Ke, Anne Barton, Steve Eyre, John Bowes, Jane Worthington, Anthony G. Wilson, Ann Morgan, Paul Emery, Sophia Steer, Lynne Hocking, David M. Reid, Paul Wordsworth, Pille Harrison, Deborah Symmons, M. Abinum, M. Becker, A. Bell, A. Craft, E. CrawleyJ. David, H. Foster, J. Gardener-Medwin, J. Griffin, A. Hall, M. Hall, A. Herrick, P. Hollingworth, L. Holt, S. Jones, G. Pountain, C. Ryder, T. Southwood, I. Stewart, H. Venning, L. Wedderburn, P. Woo, S. Wyatt, Philip Conaghan, Mark Quinn, Anne Maree Keenan, Elizabeth Hensor, Julie Kitcheman, Andrew Gough, Michael Green, Richard Reece, Lesley Hordon, Philip Helliwell, Richard Melsom, Sheelagh Doherty, Ade Adebajo, Andrew Harvey, Steve Jarrett, Gareth Huson, Amanda Isdale, Mike Martin, Zinaid Karim, Dennis McGonagle, Colin Pease, Sally Cox, Victoria Bejarano, Jackie Nam, Claire Brown, Christine Thomas, David Pickles, Alison Hammond, Beverley Neville, Alan Fairclough, Caroline Nunns, Anne Gill, Julie Green, Belinda Rhys-Evans, Barbara Padwell, Julie Madden, Lynda Taylor, Sally Smith, Heather King, Jill Firth, Jayne Heard, Linda Sigsworth, Diane Corscadden, Karen Henshaw, Lubna Haroon Rashid, Stephen G. Martin, James I. Robinson, Susan D. Thompson, Carl D. Langefeld, David N. Glass, Wendy Thomson

    Research output: Contribution to journalArticlepeer-review


    Objective. IL2RA/CD25, the gene for interleukin-2 receptor α, 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 = 4.9 × 10-5). 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. © 2009, American College of Rheumatology.
    Original languageEnglish
    Pages (from-to)251-257
    Number of pages6
    JournalArthritis Care & Research
    Issue number1
    Publication statusPublished - Jan 2009


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