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Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
  1. Gisela Orozco1,
  2. Steve Eyre1,
  3. Anne Hinks1,
  4. Xiayi Ke1,
  5. Wellcome Trust Case Control Consortium, YEAR consortium,
  6. Anthony G Wilson2,
  7. Deborah E Bax2,
  8. Ann W Morgan3,
  9. Paul Emery3,
  10. Sophia Steer4,
  11. Lynne Hocking5,
  12. David M Reid5,
  13. Paul Wordsworth6,
  14. Pille Harrison6,
  15. Wendy Thomson1,
  16. Anne Barton1,
  17. Jane Worthington1
  1. 1arc Epidemiology Unit, The University of Manchester, Manchester, UK
  2. 2School of Medicine and Biomedical Sciences, The University of Sheffield, Sheffield, UK
  3. 3NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
  4. 4Clinical and Academic Rheumatology, Kings College Hospital NHS Foundation Trust, Denmark Hill, London, UK
  5. 5Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen, UK
  6. 6University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford, UK
  1. Correspondence to Dr Gisela Orozco, arc Epidemiology Unit, Faculty of Medical and Human Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK; gisela.orozco{at}manchester.ac.uk

Abstract

Objective A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population.

Methods A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the χ2 test using Stata.

Results Association to the CD40 gene was robustly replicated (p=2×10−4, OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8×10−8, OR 0.87 (95% CI 0.83 to 0.92).

Conclusion In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.

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Footnotes

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the North West Research Ethics Committee (MREC 99/8/84).

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

    For more information on the WTCCC and YEAR Consortiums, see supplementary material.

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