The psoriasis susceptibility locus 1 (PSORS1) mutation is assumed to reside within a region around human leukocyte antigen-C spanning 250 kb, termed risk haplotype (RH) 1/2.
These data suggest that the study cohort may include a number of subjects who harbor PSORS1 predisposition to early-onset psoriasis and yet do not present with disease by the age of 40 y.
The psoriasis susceptibility 1 candidate 1 (PSORS1C1, formerly SEEK1) gene, located 127 kb telomeric to the HLA-C locus, is considered to be one of the potential candidate genes of psoriasis.
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.
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.
These results suggest that a major psoriasis susceptibility gene is likely to be located within a region of 150 kb telomeric to HLA-C and centromeric to the CDSN gene.
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.
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).
We investigated its role in susceptibility to psoriasis, the relevance of possibly other disease-causing variants, and interdependency of the major risk factor for psoriasis at PSORS1.
We confirmed that HLA-Cw*0602 positive patients have younger age of onset (17.5 vs 24.3 years, P<10(-10)), higher incidence of guttate and the eruptive type of psoriasis (P<0.0001), more frequent exacerbations with throat infections (P=0.01), higher incidence of the Koebner's phenomenon (P=0.01), and more extensive disease (P=0.03).
The risk alleles of HLA-C and CDSN (HLA-Cw6 and CDSN*TTC) were genotyped in 678 families with early-onset psoriasis; 620 of these families were also typed for 34 microsatellite markers spanning the PSORS1 interval.
The risk alleles of HLA-C and CDSN (HLA-Cw6 and CDSN*TTC) were genotyped in 678 families with early-onset psoriasis; 620 of these families were also typed for 34 microsatellite markers spanning the PSORS1 interval.
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.
The distinct HLA-C expression patterns in psoriasis and eczema suggest a functional role in the specific psoriasis immune response and not only a general feature of inflammation.
The HCR gene, officially called Coiled-Coil alpha-Helical Rod protein 1 (CCHCR1), located within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene for the risk effect.