Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus
- Gisela Orozco1,
- Steve Eyre1,
- Anne Hinks1,
- John Bowes1,
- Ann W Morgan2,
- Anthony G Wilson3,
- Paul Wordsworth4,
- Sophia Steer5,
- Lynne Hocking6,
- UKRAG consortium,
- Wendy Thomson1,
- Jane Worthington1,
- Anne Barton1
- 1Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK
- 2NIHR-Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, Leeds, UK
- 3School of Medicine and Biomedical Sciences, The University of Sheffield, Sheffield, UK
- 4Botnar Research Centre, University of Oxford Institute of Musculoskeletal Sciences, Oxford, UK
- 5Clinical and Academic Rheumatology, King's College Hospital NHS Foundation Trust, London, UK
- 6Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, UK
- Correspondence to Gisela Orozco, Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, Stopford Building, Manchester M13 9PT, UK;
- Accepted 3 October 2010
- Published Online First 10 November 2010
Background Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases.
Objective To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls.
Methods 3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test.
Results The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1×10−7) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5×10−8). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain ∼5.8% of the genetic susceptibility to RA as a whole.
Conclusion The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE.
GO and SE contributed equally to this work.
Funding This work was supported by the Arthritis Research UK (grant reference number 17552). The authors are grateful to the NIHR Manchester Biomedical Research Centre, the Wellcome Trust Case Control Consortium, NIHR-Leeds Musculoskeletal Biomedical Research Unit, the NIHR Oxford Musculoskeletal Biomedical Research Unit and the NIHR Oxford Biomedical Research Centre for support. GO is funded by the European Union (Marie Curie IEF Fellowship PIEF-GA-2009–235662).
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the MREC 99/8/84.
Provenance and peer review Not commissioned; externally peer reviewed.
UKRAG Consortium University of Manchester:1 Stephen Eyre, Anne Hinks, Laura J Gibbons, John Bowes, Edward Flynn, Paul Martin, Xiayi Ke, Rachelle Donn, Wendy Thomson, Anne Barton, Jane Worthington.
University of Leeds:2 YEAR consortium, Stephen Martin, James I Robinson, Ann W Morgan, Paul Emery
University of Sheffield:3 Anthony G. Wilson
University of London:4 Sophia Steer
University of Aberdeen:5 Lynne Hocking, David M Reid
University of Oxford:6 Pille Harrison, Paul Wordsworth
↵1 Arthritis Research UK-Epidemiology Unit, Stopford Building, The University of Manchester, Manchester, UK
↵2 Leeds Institute of Molecular Medicine, Section of Musculoskeletal Disease, University of Leeds, Leeds LS9 7TF, UK
↵3 School of Medicine and Biomedical Sciences, The University of Sheffield, Sheffield S10 2JF, UK.
↵4 Clinical and Academic Rheumatology, Kings College Hospital NHS Foundation Trust, Denmark Hill, London SE5 9RS, UK
↵5 Bone Research Group, Department of Medicine and Therapeutics, University of Aberdeen AB25 2ZD, UK
↵6 University of Oxford Institute of Musculoskeletal Sciences, Botnar Research Centre, Oxford OX3 7LD, UK
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