After controlling for the age of psoriasis onset no association of PsA to HLA-C*06:02 (p=0.07) was observed; instead, the most significant association was to amino acid at position 97 of HLA-B (p=1.54×10<sup>-9</sup>) where the presence of asparagine or serine residue increased PsA risk.
Also, as a 'proof of principle' calculation, we perform power and sample size calculations for all genes within 100 kb of the PSORS1 locus (chromosome 6) for a previously published association study of psoriasis.
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).
Although several additional genes remain to be identified, the variants that have so far been described support the autoimmune basis of psoriasis indicating that the disease may be mediated by T-cells reacting against (self)antigen(s) in the binding pocket of HLA-C, with contribution from the recently described Th17 subset of T-cells which are maintained by the IL-23 cytokine axis.
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)].
Among identified psoriasis risk variants, three were more strongly associated with PsC than PsA (rs12189871 near HLA-C, p = 5.0 × 10(-19); rs4908742 near TNFRSF9, p = 0.00020; rs10888503 near LCE3A, p = 0.0014), and two were more strongly associated with PsA than PsC (rs12044149 near IL23R, p = 0.00018; rs9321623 near TNFAIP3, p = 0.00022).
Amongst patients with psoriatic arthritis, those who carried the HLA-Cw*0602 allele had a significantly earlier mean age of onset of their psoriasis (p = 0.003).
An analysis of the linkage disequilibrium and stratification also indicated that the alleles of TAP and HLA-DM might be independently associated with HLA-Cw*0602 in psoriasis patients.
An association study of the new HCR polymorphisms and the previously suggested susceptibility alleles HLA-Cw*0602 and corneodesmosin allele 5 (CD*5) with psoriasis revealed a specific HCR variant associated with psoriasis susceptibility.
An ERAP1 haplotype known to possess high enzymatic activity was associated with psoriasis if HLA-C*06:02 was present and a functional ERAP2 allele was absent.
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.
Based on a nationwide collection of psoriasis patients and genotyping for the PSORS1 susceptibility haplotype, we selected for a genome scan nine families who do not show association with PSORS1 to more easily detect minor loci for psoriasis susceptibility.
Besides the HLA-Cw*0602 allele, the psoriasis susceptibility 1 candidate 3 (PSORS1C3) and corneodesmosin (CDSN) genes are two probable psoriasis susceptibility genes in the PSORS1 locus.
By applying the transmission/disequilibrium test (TDT) and parametric linkage analysis, we found evidence for linkage of psoriasis to HLA-C, -B, -DR, and -DQ, with HLA-B and -C yielding the most-significant results.
Case-control analysis revealed an association of IL12B rs3212227 and IL23R rs11209026 minor allele carrier status with reduced odds for psoriasis (OR = 0.66, 95%CI: 0.50-0.87, and OR = 0.41, 95%CI: 0.26-0.67, respectively), while HLA-C*06 allele carriers were more frequent in patients group (OR = 4.56, 95%CI: 3.41-6.10).
CCHCR1 (Coiled-Coil α-Helical Rod protein 1), within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene with the psoriasis associated risk allele CCHCR1*WWCC.
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.
Comparing PsA and psoriasis, the prevalence of HLA-B*27 and HLA-Cw*12 were more common in PsA patients, while the prevalence of HLA-DR*07 was higher in those with psoriasis (p < 0.05).
Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis.