Genomic structure, promoter characterisation and mutational analysis of the S100A7 gene: exclusion of a candidate for familial psoriasis susceptibility

We have recently assigned a locus for familial psoriasis (PS) susceptibilit y to the region containing the epidermal differentiation complex gene clust er on chromosome 1q21. Gene S100A7 maps within this cluster and is reported to be markedly over-expressed in the skin lesions of psoriatic patients. I n order to analyse S100A7 as a candidate we have determined its genomic for PS susceptibility, structure regarding exon-intron boundaries and the tran scription start site. The gene is organised in three exons and two introns, spanning 2.7 kb. The 5' flanking region contains AP1- and Sp1-binding moti fs and a TATA box. We have performed functional assays by using the beta-ga lactosidase gene as a reporter and have confirmed that this region has stro ng promoter activity. To starch for nucleotide variation within S100A7, we have designed a set of primers to amplify each exon and the gene promoter. Polymerase chain reaction products from 15 unrelated PS patients selected f rom 1q-linked pedigrees and 25 normal controls have been characterised by s ingle-strand conformation polymorphism and direct sequencing techniques, Th ese analyses have revealed the presence of two polymorphisms in the promote r region (-559G/A and -563 A/G), neither of which shows preferential associ ation with the disease. Our results indicate that S100A7 can be excluded as a candidate for PS susceptibility.