Article Text
Abstract
Objectives Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.
Methods Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.
Results Thirteen SNP showed significant association (p<0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.
Conclusions A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.
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Footnotes
↵* Members of the Childhood Arthritis Prospective Study (CAPS), UKRAG Consortium and the British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group are shown at the end of the paper
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Childhood Arthritis Prospective Study (CAPS) Eileen Baildam, Lynsey Brown, Joanne Buckley, Alice Chieng, Joyce Davidson, Michael Eltringham, Helen Foster, Mark Friswell, Janet Gardner-Medwin, Paul Gilbert, KimmeHyrich, Julie Jones, Sham Lal, Mark Lay, Carol Lydon, Alexandra Meijer, Vicki Price, Jane Sim, Maureen Todd, Peter Ward, Lucy Wedderburn.
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UKRAG Consortium Arthritis Research UK Epidemiology Unit, University of Manchester: Stephen Eyre, Anne Hinks, John Bowes, Edward Flynn, Paul Martin, Wendy Thomson, Anne Barton, Jane Worthington; Leeds Institute of Molecular Medicine, Section of Musculoskeletal Disease, University of Leeds: Stephen Martin, James I Robinson, Ann W Morgan, Paul Emery; School of Medicine and Biomedical Sciences, University of Sheffield: Anthony G. Wilson; Clinical and Academic Rheumatology, Kings College Hospital NHS Foundation Trust, University of London: Sophia Steer; Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen: Lynne Hocking, David M Reid; University of Oxford Institute of Musculoskeletal Sciences, University of Oxford: Pille Harrison, Paul Wordsworth
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British Society of Paediatric and Adolescent Rheumatology (BSPAR) Study Group M Abinum, M Becker, A Bell, A Craft, E Crawley, J 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
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Funding This work was supported by Arthritis Research UK grant reference no. 17552 and the National Institutes of Health (RC1-AR-058587, P30-AR-473639 to SDT, K23-AR-50177 to SP, R01-AR-057106 to CDL and SDT, P01-AR048929 and N01-AR-42272 to DNG); the Federal Ministry of Education and Research Germany (BMBF) (grants 01GM0907 and 01 ZZ 0403 to JPH); the Val A. Browning Foundation; the Texas Scottish Rite Hospital for Children (grant 0305756 to CW and MP); and the Arthritis Foundation.
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Ethics approval Ethics approval was obtained from the North-West Multi-Centre Research Ethics Committee (MREC 99/8/84) and the University of Manchester Committee on the Ethics of Research on Human Beings.
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Patient consent Obtained.
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Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.