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PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian Population
  1. Marian L Burr (marianlburr{at}doctors.org.uk)
  1. University of Manchester, United Kingdom
    1. Haris Naseem (harisnaseem{at}doctors.org.uk)
    1. University of Manchester, United Kingdom
      1. Anne Hinks (a.m.hinks{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. Laura Gibbons (laura.gibbons{at}manchester.ac.uk)
          1. University of Manchester, United Kingdom
            1. John Bowes (j.bowes{at}manchester.ac.uk)
            1. University of Manchester, United Kingdom
              1. BIRAC Consortium
              1. BIRAC Consortium, United Kingdom
                1. YEAR Consortium
                1. YEAR Consortium, United Kingdom
                  1. Anthony G Wilson (a.g.wilson{at}sheffield.ac.uk)
                  1. University of Sheffield, United Kingdom
                    1. James Maxwell (j.maxwell{at}sheffield.ac.uk)
                    1. University of Sheffield, United Kingdom
                      1. Ann W Morgan (a.w.morgan{at}leeds.ac.uk)
                      1. University of Leeds, United Kingdom
                        1. Paul Emery (p.emery{at}leeds.ac.uk)
                        1. University of Leeds, United Kingdom
                          1. Sophia Steer (sophia.2.steer{at}kcl.ac.uk)
                          1. Kings College 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. B Paul Wordsworth (paul.wordsworth{at}ndm.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. Jane Worthington (jane.worthington{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

                                          Abstract

                                          Background: Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asians. However, studies in European populations have produced conflicting results. This study explored the association of PADI4 genotype with RA in a large UK Caucasian population.

                                          Methods: The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian RA patients (n=3,732) and population controls (n=3,039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was utilised to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1,859) and controls (n=10,599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study.

                                          Results: PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all RA cases (n=5,591) and controls (n=13,638) gave an overall OR of 1.01 (0.96-1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between PADI4_94 genotype and RA in people of European descent (OR 1.06, 0.99-1.13, p=0.12).

                                          Conclusion: In the largest study performed to date, we found that, in contrast to Asian populations, PADI4 genotype is not a significant risk factor for RA in people of European ancestry.

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