Genetic analysis of PSORS1 distinguishes guttate psoriasis and palmoplantar pustulosis

The PSORS1 locus in the major histocompatibility complex region is the major genetic determinant for psoriasis vulgaris. Within the PSORS1 region reside at least three potential candidate genes for psoriasis susceptibility. Specific allelic variants of the genes HLA-Cw*6, HCR*WWCC, and CDSN*5 are strongly associated with psoriasis vulgaris and are in strong linkage disequilibrium with each other. We have genotyped the three psoriasis vulgaris susceptibility alleles of the PSORS1 locus in two clinical variants of psoriasis (guttate psoriasis and palmoplantar pustulosis) to study whether PSORS1 is also involved in the pathogenesis of these variants. We also asked whether these two clinical subgroups could help us to distinguish the causative gene within the high-risk PSORS1 haplotype. The association of guttate psoriasis with the three PSORS1 susceptibility alleles was similar and even stronger than seen with psoriasis vulgaris. Palmoplantar pustulosis, however, did not show association with any of the three candidate genes at this locus. Finally, no correlation with the age of onset for disease was observed. Our results show conclusively that psoriasis vulgaris and guttate psoriasis have a similar genetic basis for their association to PSORS1, whereas palmoplantar pustulosis appears to be a distinct disorder.