Association analysis using refined microsatellite markers localizes a susceptibility locus for psoriasis vulgaris within a 111 kb segment telomeric to the HLA-C gene

The HLA-Cw6 antigen has been associated with psoriasis vulgaris despite rac ial and ethnic differences, However, it remains unclear whether it is the H LA-Cw6 antigen itself or a closely linked, hitherto unidentified, locus tha t predisposes to the disease. Here, in order to map the susceptibility locu s for psoriasis vulgaris precisely within the HLA class I region, 11 polymo rphic microsatellite markers distributed throughout a 1060 kb segment surro unding the HLA-C locus were subjected to association analysis in Japanese p soriasis vulgaris patients, Statistical analyses of the distribution and de viation from Hardy-Weinberg equilibrium of the allelic frequency at each mi crosatellite locus revealed that the pathogenic gene for psoriasis vulgaris is located within a reduced interval of 111 kb spanning 89-200 kb telomeri c of the HLA-C gene, In addition to three known genes, POU5F1, TCF19 and S, this 111 kb fragment contains four new, expressed genes identified in the course of our genomic sequencing of the entire HLA class I region, Therefor e, these seven genes are the potential candidates for susceptibility to pso riasis vulgaris.