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

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 = 2.2 x 10(-21)) and with patients with PsA having type I psoriasis (OR 5.0, 95% CI 3.2, 7.9, p = 4.39 x 10(-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.