Article Text

This article has a correction. Please see:

other Versions

PDF
Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study
  1. Gisela Orozco (gisela.orozco{at}manchester.ac.uk)
  1. University of Manchester, United Kingdom
    1. Steve Eyre (steve.eyre{at}manchester.ac.uk)
    1. University of Manchester, United Kingdom
      1. Anne Hinks (anne.hinks{at}manchester.ac.uk)
      1. University of Manchester, United Kingdom
        1. Xiayi Ke (xiayi.ke{at}manchester.ac.uk)
        1. University of Manchester, United Kingdom
          1. Anthony G Wilson (a.g.wilson{at}sheffield.ac.uk)
          1. University of Sheffield, United Kingdom
            1. Deborah E Bax (d.e.bax{at}sheffield.ac.uk)
            1. University of Sheffield, United Kingdom
              1. Ann W Morgan (a.w.morgan{at}leeds.ac.uk)
              1. Leeds Institute of Molecular Medicine, United Kingdom
                1. Paul Emery (p.emery{at}leeds.ac.uk)
                1. Dept of Rheumatology, United Kingdom
                  1. Sophia Steer (sophia.2.steer{at}kcl.ac.uk)
                  1. Kings College Hospital London, United Kingdom
                    1. Lynne Hocking (l.hocking{at}abdn.ac.uk)
                    1. University of Aberdeen, United Kingdom
                      1. David M Reid (d.m.reid{at}abdn.ac.uk)
                      1. University of Aberdeen, United Kingdom
                        1. Paul Wordsworth (paul.wordsworth{at}ndos.ox.ac.uk)
                        1. University of Oxford, United Kingdom
                          1. Pille Harrison (pille.harrison{at}ndos.ox.ac.uk)
                          1. University of Oxford, United Kingdom
                            1. Wendy Thomson (wendy.thomson{at}manchester.ac.uk)
                            1. University of Manchester, United Kingdom
                              1. Anne Barton (anne.barton{at}manchester.ac.uk)
                              1. University of Manchester, United Kingdom
                                1. Jane Worthington (jane.worthington{at}manchester.ac.uk)
                                1. University of Manchester, United Kingdom

                                  Abstract

                                  Objective: A recent meta-analysis of published genome wide association studies (GWASs) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with RA susceptibility whilst 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: Four SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3,962 UK RA cases and 3,531 healthy controls using the Sequenom iPlex platform. Genotype counts in cases and controls were analysed using the chi squared test using Stata.

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

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

                                  Statistics from Altmetric.com

                                  • Web Only Data ard.2009.109579

                                    Files in this Data Supplement:

                                  Request permissions

                                  If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.