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PSORS1  (psoriasis susceptibility gene 1) is a major susceptibility locus for psoriasis. Several fine-mapping studies have highlighted a 300-kb candidate region of  PSORS1  where multiple biologically plausible candidate genes were suggested. The most recent study has indicated  HLA-Cw6  as the primary  PSORS1  risk allele within the candidate region in a Caucasian population. In this study, a family-based association analysis of the  PSORS1  locus was performed by analyzing 10 polymorphic microsatellite markers from the  PSORS1  region as well as  HLA-B ,  HLA-C  and  CDSN  loci in 163 Chinese families of psoriasis. Five marker loci show strong evidence (P<10 −3 ), and one marker locus shows weak evidence (P = 0.04) for association. The haplotype cluster analysis showed that all the risk haplotypes are  Cw6  positive and share a 369-kb region of homologous marker alleles which carries all the risk alleles, including  HLA-Cw6  and  CDSN*TTC , identified in this study. The recombinant haplotype analysis of the  HLA-Cw6  and  CDSN*TTC  alleles in 228 Chinese families showed that the  HLA-Cw6   − / CDSN*TTC   +  recombinant haplotype is clearly not associated with risk for psoriasis (T∶NT = 29:57, p = 0.0025) in a Chinese population, suggesting that the  CDSN*TTC  allele itself does not confer risk without the presence of the  HLA-Cw6  allele. The further exclusion analysis of the non-risk  HLA-Cw6   − / CDSN*TTC   +  recombinant haplotypes with common recombination breakpoints has allowed us to refine the location of  PSORS1  to a small candidate region. Finally, we performed a conditional linkage analysis and showed that the  HLA-Cw6  is a major risk allele but does not explain the full linkage evidence of the  PSORS1  locus in a Chinese population. By performing a series of family-based association analyses of haplotypes as well as an exclusion analysis of recombinant haplotypes, we were able to refine the  PSORS1  gene to a small critical region where  HLA-C  is a strong candidate to be the  PSORS1  susceptibility gene.

Fine Mapping of the Psoriasis Susceptibility Locus PSORS1 Supports HLA-C as the Susceptibility Gene in the Han Chinese Population