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Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis: comparison with psoriasis and undifferentiated inflammatory arthritis
  1. Pauline YPC Ho (pauline.ho{at}manchester.ac.uk)
  1. University of Manchester, United Kingdom
    1. Anne Barton (anne.barton{at}manchester.ac.uk)
    1. The University of Manchester, United Kingdom
      1. Jane Worthington (jane.worthington{at}manchester.ac.uk)
      1. The University of Manchester, United Kingdom
        1. Darren Plant (darren.plant{at}manchester.ac.uk)
        1. The University of Manchester, United Kingdom
          1. Christopher EM Griffiths (christopher.griffiths{at}manchester.ac.uk)
          1. Dermatology Centre, Hope Hospital, The University of Manchester, United Kingdom
            1. Helen S Young (helen_s_young{at}hotmail.com)
            1. Dermatology Centre, Hope Hospital, The University of Manchester, United Kingdom
              1. Peter Bradburn (p.bradburn{at}bham.ac.uk)
              1. Dept of Public Health and Epidemiology, University of Birmingham, United Kingdom
                1. Wendy Thomson (wendy.thomson{at}manchester.ac.uk)
                1. The University of Manchester, United Kingdom
                  1. Alan J Silman (alan.silman{at}manchester.ac.uk)
                  1. The University of Manchester, United Kingdom
                    1. Ian N Bruce (ian.bruce{at}manchester.ac.uk)
                    1. The University of Manchester, United Kingdom

                      Abstract

                      Objective: Psoriasis of early onset (Type I; age of onset ≤ 40years) is associated with HLA-Cw*06 whilst the shared epitope (SE) is associated with rheumatoid arthritis (RA) susceptibility. Our aim was to investigate the role of HLA-Cw*06 and HLA-DRB1 genes (including SE) with psoriatic arthritis (PsA) susceptibility.

                      Methods: In a case-control association study, HLA-Cw*06 phenotype frequencies were compared between patients with PsA (n = 480), psoriasis alone (n = 611) and healthy controls (n = 166). Similarly, at the HLA-DRB1 locus, phenotype and SE frequencies were compared in patients with PsA (n = 480), early undifferentiated inflammatory arthritis (UIA) alone (n = 1621) and healthy controls (n = 537).

                      Results: The HLA-Cw*06 phenotype was associated with Type I psoriasis (OR 6.9, 95% CI 4.4, 11.1, p=2.2x10-21) and with PsA patients having type I psoriasis (OR 5.0, 95% CI 3.2, 7.9, p = 4.39x10-13), but not with PsA patients having type II psoriasis (age of onset >40 years). HLA-DRB1*07, in linkage disequilibrium with HLA-Cw*06, was also associated with PsA patients having type I psoriasis (OR 2.7, 95% CI 2.1, 3.7, p<0.00001). HLA-DRB1*04 alleles and the SE were associated with UIA but not with PsA.

                      Conclusion: The SE is not a PsA susceptibility locus. HLA-Cw*06 and HLA-DRB1*07 are associated with PsA patients having type I psoriasis, suggesting that the primary association is with age of onset of psoriasis. PsA patients having type I psoriasis, therefore, have a different genetic background to those with type II psoriasis and adjustment for this is necessary in future studies that investigate the genetic susceptibility of PsA.

                      • HLA-Cw*06
                      • HLA-DRB1
                      • HLA-DRB1*07
                      • psoriasis
                      • psoriatic arthritis

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