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Ann Rheum Dis 69:2169-2172 doi:10.1136/ard.2009.126938
  • Clinical and epidemiological research
  • Concise report

Investigation of type 1 diabetes and coeliac disease susceptibility loci for association with juvenile idiopathic arthritis

Open Access
  1. Wendy Thomson1
  1. 1Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, UK
  2. 2Haywood Hospital, University Hospital of North Staffordshire, Stoke on Trent, Staffordshire, ST4 7LN
  1. Correspondence to Dr Anne Hinks, Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, Stopford Building, The University of Manchester, Manchester M13 9PT, UK; anne.hinks{at}manchester.ac.uk
  • Accepted 25 June 2010
  • Published Online First 20 July 2010

Abstract

Background There is strong evidence suggesting that juvenile idiopathic arthritis (JIA) shares many susceptibility loci with other autoimmune diseases.

Objective To investigate variants robustly associated with type 1 diabetes (T1D) or coeliac disease (CD) for association with JIA.

Methods Sixteen single-nucleotide polymorphisms (SNPs) already identified as susceptibility loci for T1D/CD were selected for genotyping in patients with JIA (n=1054) and healthy controls (n=3129). Genotype and allele frequencies were compared using the Cochrane–Armitage trend test implemented in PLINK.

Results One SNP in the LPP gene, rs1464510, showed significant association with JIA (ptrend=0.002, OR=1.18, 95% CI 1.06 to 1.30). A second SNP, rs653178 in ATXN2, also showed nominal evidence for association with JIA (ptrend=0.02, OR=1.13, 95% CI 1.02 to 1.25). The SNP, rs17810546, in IL12A showed subtype-specific association with enthesitis-related arthritis (ERA) subtype (ptrend=0.005, OR=1.88, 95% CI 1.2 to 2.94).

Conclusions Evidence for a novel JIA susceptibility locus, LPP, is presented. Association at the SH2B3/ATXN2 locus, previously reported to be associated with JIA in a US series, also supports this region as contributing to JIA susceptibility. In addition, a subtype-specific association of IL12A with ERA is identified. All findings will require validation in independent JIA cohorts.

Footnotes

  • Childhood arthritis prospective study (CAPS) group Eileen Baildam, Lynsey Brown, Joanne Buckley, Alice Chieng, Joyce Davidson, Michael Eltringham, Helen Foster, Mark Friswell, Janet Gardner-Medwin, Paul Gilbert, Kimme Hyrich, Julie Jones, Sham Lal, Mark Lay, Carol Lydon, Alexandra Meijer, Vicki Price, Jane Sim, Maureen Todd, Peter Ward, Lucy Wedderburn.

  • UKRAG Consortium Stephen Eyre, Anne Hinks, John Bowes, Gisela Orozco, Edward Flynn, Paul Martin, Wendy Thomson, Anne Barton, Jane Worthington: Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, Stopford Building, The University of Manchester, Manchester, UK; Stephen Martin, James I Robinson, Ann W Morgan, Paul Emery: Leeds Institute of Molecular Medicine, Section of Musculoskeletal Disease, University of Leeds, Leeds LS9 7TF, UK; Anthony G Wilson: School of Medicine and Biomedical Sciences, The University of Sheffield, Sheffield S10 2JF, UK; Sophia Steer: Clinical and Academic Rheumatology, Kings College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK; Lynne Hocking, David M Reid: Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen AB25 2ZD, UK; Pille Harrison, Paul Wordsworth: University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, UK.

  • British Society of Paediatric and Adolescent Rheumatology (BSPAR) study group M Abinum, MD, M Becker, MD, A Bell, MD, A Craft, MD, E Crawley, MD, J David, MD, H Foster, MD, J Gardener-Medwin, MD, J Griffin, MD, A Hall, MD, M Hall, MD, A Herrick, MD, P Hollingworth, MD, L Holt, MD, S Jones, MD, G Pountain, MD, C Ryder, MD, T Southwood, MD, I Stewart, MD, H Venning, MD, L Wedderburn, MD, P Woo, MD, and S Wyatt, MD.

  • Funding This work was supported by Arthritis Research UK: AR UK grant reference No 17552. The authors would like to thank David Strachan for facilitating access to the 1958 Birth Cohort. The authors acknowledge use of genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. The authors acknowledge support from the NIHR Manchester Biomedical Research Council.

  • Ethics approval This study was conducted with the approval of 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).

  • Provenance and peer review Not commissioned; externally peer reviewed.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl