Identification of six novel polymorphisms in the human corneodesmosin gene

Psoriatic epidermis is characterised by a defective differentiation program leading to an abnormal permeability barrier and impaired desquamation The corneodesmosin gene (CDSN) or "S" gene is a strong candidate in psoriasis s usceptibility, due first to its genomic position ("S" gene, 160 kb telomeri c to HLA-C) and second to its expression and function in the epidermis. Mor eover, an association between CDSN and psoriasis vulgaris was recently show n in Caucasian populations, In order to pursue the CDSN polymorphism analys is se determined the sequence of its alleles in 14 HLA-Cw6-positive individ uals. A 4.6 kb genomic fragment encompassing the first exon, the unique int ron and the coding sequence of the second exon was amplified from 8 psoriat ic patients and 6 controls Allelic discrimination was performed by restrict ion fragment length polymorphism analysis. The entire coding sequence and t he intron boundaries of 27 alleles were sequenced. A total of 26 dimorphic sites were found, 23 consisting in single nucleotide polymorphisms (SNPs) a nd 3 in triplet modifications. Five out of the 23 SNPs have not been previo usly reported, and among them, one causes amino-acid exchange leading to th e suppression of a potential chymotrypsin site. Among the triplet modificat ions, one leads to deletion of one out of five consecutive valines in the p rotein. The high polymorphism of the gene allowed the identification of 13 different alleles. These haplotypes will permit additional family-based stu dies that could provide new genetic support for the involvement of CDSN in psoriasis susceptibility, Moreover, the establishment of an extensive catal ogue of CDSN alleles will allow functional analyses of the different protei n isoforms.