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 <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.
Ho
P Y P C
PY
Epidemiology Unit, Stopford Building, University of Manchester, Manchester, UK.
Barton
A
A
Worthington
J
J
Plant
D
D
Griffiths
C E M
CE
Young
H S
HS
Bradburn
P
P
Thomson
W
W
Silman
A J
AJ
Bruce
I N
IN
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D015535:Arthritis, Psoriatic / Q000235:genetics*; D016918:Arthritis, Reactive / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics
D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen; C456920:HLA-DRB1*07 antigen; D016056:Immunodominant Epitopes