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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
Ho, PY, Barton, A, Worthington, J, Plant, D, Griffiths,C.E., Young,H.S., Bradburn, P, Thomson, W, Silman, AJ, Bruce, IN
Annals of the Rheumatic Diseases. 2008;67(5):677-682.
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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
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- DA - 20070830IS - 0003-4967 (Print)LA - ENGPT - JOURNAL ARTICLE