Ann Rheum Dis

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Published Online First: 29 August 2007. doi:10.1136/ard.2007.071399
Annals of the Rheumatic Diseases 2008;67:677-682
Copyright © 2008 BMJ Publishing Group Ltd & European League Against Rheumatism

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EXTENDED REPORTS

Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis: comparison with psoriasis and undifferentiated inflammatory arthritis

P Y P C Ho 1, A Barton 1, J Worthington 1, D Plant 1, C E M Griffiths 2, H S Young 2, P Bradburn 3, W Thomson 1, A J Silman 1, I N Bruce 1

1 arc-Epidemiology Unit, Stopford Building, University of Manchester, Manchester, UK
2 Dermatology Centre, Hope Hospital, University of Manchester, Manchester, UK
3 Department of Public Health and Epidemiology, University of Birmingham, UK

Correspondence to:
Pauline Ho, arc-EU, Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT, UK; Pauline.Ho{at}manchester.ac.uk

Objective: Psoriasis of early onset (type I; age of onset <=40 years) is associated with HLA-Cw*06 while the shared epitope (SE) is associated with rheumatoid arthritis 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 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 patients with PsA having type I psoriasis (OR 5.0, 95% CI 3.2, 7.9, p = 4.39x10–13), but not with patients with PsA having type II psoriasis (age of onset >40 years). HLA-DRB1*07, in linkage disequilibrium with HLA-Cw*06, was also associated with patients with PsA 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 undifferentiated inflammatory arthritis but not with PsA.

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








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