PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population
- Marian L Burr1,
- Haris Naseem1,
- Anne Hinks1,
- Steve Eyre1,
- Laura J Gibbons1,
- John Bowes1,
- Anthony G Wilson2,
- James Maxwell2,
- Ann W Morgan3,
- Paul Emery3,
- Sophia Steer4,
- Lynne Hocking5,
- David M Reid5,
- Paul Wordsworth6,
- Pille Harrison6,
- Wendy Thomson1,
- Jane Worthington1,
- BIRAC Consortium7,
- YEAR Consortium8,
- Anne Barton1
- 1arc-Epidemiology Unit, University of Manchester, Manchester, UK
- 2School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK
- 3Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, UK
- 4Clinical and Academic Rheumatology, King's College Hospital NHS Foundation Trust, London, UK
- 5Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen, UK
- 6University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford, UK
- 7BIRAC Consortium
- 8YEAR Consortium
- Correspondence to Dr Anne Barton, arc-Epidemiology Unit, Stopford Building, Oxford Road, University of Manchester, Manchester M13 9PT, UK;
- Accepted 10 May 2009
- Published Online First 25 May 2009
Background Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the 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 patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) 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 The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 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 the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12).
Conclusion In the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations.
Competing interests None.
Ethics approval This study was conducted with the approval of the North West Research ethics committee (MREC 99/9/84).
Provenance and peer review Not commissioned; externally peer reviewed.
Membership of the BIRAC Consortium and YEAR Consortium is shown in the online supplement.
This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl