Fine mapping of the psoriasis susceptibility locus PSORS1 supports HLA-C as the susceptibility gene in the Han...

Area of Science:

• Genetics
• Immunology
• Dermatology

Background:

• Psoriasis susceptibility gene 1 (PSORS1) is a major genetic locus associated with psoriasis.
• Previous studies identified a candidate region and suggested HLA-Cw6 as a primary risk allele in Caucasians.

Purpose of the Study:

• To perform family-based association analysis of the PSORS1 locus in a Chinese population.
• To refine the PSORS1 critical region and identify susceptibility genes.
• To investigate the role of HLA-Cw6 and CDSN*TTC alleles in psoriasis risk.

Main Methods:

• Analyzed 10 microsatellite markers, HLA-B, HLA-C, and CDSN loci in 163 Chinese psoriasis families.
• Conducted haplotype cluster and recombinant haplotype analyses.
• Performed conditional linkage and exclusion analyses.

Main Results:

• Five marker loci showed strong association (P<10(-3)) with psoriasis.
• Risk haplotypes were HLA-Cw6 positive and shared a 369-kb region including HLA-Cw6 and CDSN*TTC.
• The HLA-Cw6(-)/CDSN*TTC(+) haplotype was not associated with risk, indicating CDSN*TTC requires HLA-Cw6.
• Exclusion analysis refined PSORS1 to a small region, with HLA-C as a strong candidate.

Conclusions:

• HLA-Cw6 is a major psoriasis risk allele in the Chinese population.
• The PSORS1 critical region is refined, implicating HLA-C as a strong candidate susceptibility gene.
• Further investigation is needed to fully explain the linkage evidence for PSORS1 in this population.