title: Evidence for differential S100 gene over-expression in psoriatic patients from genetically heterogeneous pedigrees.
abstract: Psoriasis is an inflammatory skin disorder characterised by keratinocyte hyper-proliferation and altered differentiation. To date, linkage analyses have identified at least seven distinct disease susceptibility regions (PSORS1-7). The PSORS4 locus was mapped by our group to chromosome 1q21, within the Epidermal Differentiation Complex. This cluster contains 13 genes encoding S100 calcium-binding proteins, some of which ( S100A7, S100A8 and S100A9) are known to be up-regulated in individual patient keratinocytes. In this study, we analysed S100 gene expression in psoriatic individuals from families characterised by linkage studies. We first selected individuals from two large pedigrees, one of which was linked to the 1q21 locus, whereas the other was unlinked to that region. We studied the expression of 12 S100 genes, by semi-quantitative RT-PCR and Northern blot. These analyses demonstrated up-regulation of S100A8, S100A9 and, to a lesser extent, S100A7 and S100A12, only in the 1q21 linked family. We subsequently analysed S100A7, S100A8, S100 A9 and S100 A12 in three additional samples and were able to confirm S100A8/ S100A9-specific over-expression in 1q-linked pedigrees. Thus, our data provide preliminary evidence for a locus-specific molecular mechanism underlying psoriasis susceptibility.
authors.affiliation: Cattedra di Genetica, Edificio E Nord, piano terra, Università di Roma Tor Vergata, via di Tor Vergata 135, 00133 Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Semprini
authors.forename: Francesca
authors.initials: F
authors.lastname: Capon
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tacconelli
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giardina
authors.forename: Angela
authors.initials: A
authors.lastname: Orecchia
authors.forename: Rita
authors.initials: R
authors.lastname: Mingarelli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gobello
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zambruno
authors.forename: Annalisa
authors.initials: A
authors.lastname: Botta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fabrizi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
mesh_terms: D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D010375:Pedigree; D011565:Psoriasis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009418:S100 Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D009418:S100 Proteins