Certain HLA-B and HLA-C alleles confer susceptibility to PsA among patients with psoriasis and may be used to identify patients with PsC who may develop PsA.
And it is interesting that a missense mutation in SPRED1 and a splice region mutation in C3 are found in the psoriasis individuals in the other two MZ twin pairs without carrying HLA-C*0602 allele.
: No allele was associated with absence of recurrence in patients receiving adjuvant interferon with the exception ofHLA-Cw 06, an allele correlated with psoriasis.
HLA-C alleles of 89 patients with psoriasis with onset at the age of 40 y or later and 80 control subjects were determined by a polymerase chain reaction (PCR), low-resolution method.
Patients who carried the HLA-Cw*06 allele had a significantly earlier mean age of onset of both psoriasis (P = 0.01) and arthritis (P = 0.008) compared with Cw*06-negative patients.
These data demonstrate the power of SNP haplotype-based association analyses and provide high-resolution dissection of genetic variation across the PSORS1 interval, the major susceptibility locus for psoriasis.
Furthermore, when combining the results of both the stepwise regression analysis and the HLA-C*06:02 conditioning analysis, different variants were found to be independently associated with each psoriasis subgroup.
Very recent data strongly indicate that HLA-Cw*0602 is the susceptibility allele in this locus, a finding that is consistent with the notion that the pathogenesis of psoriasis involves autoantigen recognition by epidermal CD8+ T lymphocytes.
Among cases of psoriasis, it was noted that there was a significant association of HLA-C*06 positivity with female psoriatics [p = 0.006; OR 2.49 (1.28-4.87)] and early age of onset of psoriasis [p = 0.002; OR 2.04 (1.29-3.20)].
Although a psoriasis susceptibility gene(s) has not been yet identified, a number of candidate genes were studied, with evidence for a major locus located within the major histocompatibility complex (PSORS 1).
Moreover, we need to determine allele-specific effects of ERAP1 variants in the context of HLA-B*51 and HLA-Cw*6, which are associated with Behçet's disease and psoriasis, respectively.
I review two examples of such challenges: the cloning of GPR154 (GPRA) and AAA1 on chromosome 7p14 at a susceptibility locus for atopy and asthma, and the study of HLA-Cw6, CCHCR1 (HCR) and CDSN on chromosome 6p21 at PSORS1, the major susceptibility locus for psoriasis.
Similar to AS, the strongest genetic signal of susceptibility to psoriasis and psoriatic arthritis also emanates from the MHC region (attributable mostly to HLA-C(*)06:02 although other genes have been implicated), and gene-gene interaction of HLA-C with ERAP1.
After adjusting for significant HLA-B and HLA-C alleles in multivariate analyses, MICA*016 remained significantly associated with psoriasis [odds ratio (OR) = 5.5, P = 0.008].
Of note, these 'MHC-I-opathies' show a differential immunopathology, probably reflecting antigenic differences within target tissues: HLA-B(*)51 is linked to ocular and mucocutaneous disease but not gut involvement, and HLA-C(*)0602 is linked to type I psoriasis but not scalp or nail disease.