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.
- psoriatic arthritis