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OBJECTIVE: Psoriasis of early onset (type I; age of onset <or=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.

Type

Journal article

Journal

Annals of the rheumatic diseases

Publication Date

05/2008

Volume

67

Pages

677 - 682

Addresses

Epidemiology Unit, Stopford Building, University of Manchester, Manchester, UK.

Keywords

Humans, Arthritis, Reactive, Arthritis, Psoriatic, Psoriasis, Genetic Predisposition to Disease, HLA-C Antigens, HLA-DR Antigens, Immunodominant Epitopes, Case-Control Studies, Age of Onset, Gene Frequency, Genotype, Alleles, Adolescent, Adult, Middle Aged, Female, Male, Genetic Linkage, HLA-DRB1 Chains