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

Abstract

We have recently assigned a locus for familial psoriasis (PS) susceptibility to the region containing the epidermal differentiation complex gene cluster on chromosome 1q21. Gene S10OA7 maps within this cluster and is reported to be markedly over-expressed in the skin lesions of psoriatic patients. In order to analyse S100A7 as a candidate for PS susceptibility, we have determined its genomic structure regarding exon-intron boundaries and the transcription 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 motifs and a TATA box. We have performed functional assays by using the beta-galactosidase gene as a reporter and have confirmed that this region has strong promoter activity. To search 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 from 1q-linked pedigrees and 25 normal controls have been characterised by single-strand conformation polymorphism and direct sequencing techniques. These analyses have revealed the presence of two polymorphisms in the promoter region (-559G/A and -563 A/G), neither of which shows preferential association with the disease. Our results indicate that S100A7 can be excluded as a candidate for PS susceptibility.

Selective expression of S100A7 in lung squamous cell carcinomas and large cell carcinomas but not in adenocarcinomas and small cell carcinomas

“…S100A7 was originally identified as a protein whose expression was increased in psoriatic keratinocytes 9. Later studies have shown that S100A7 could play an important role in antibacterial action10 and its overexpression is prominently associated with early stages of various carcinomas, including squamous carcinomas in skin and bladder, and ductal in situ carcinomas and adenocarcinomas of the breast 11 – 16. Expression of S100A7 is often diminished in carcinomas during their progression to invasive carcinoma.…”

The role of IL-36γ/IL-1F9 in developing erythroderma in patients with psoriasis

“…К сожалению, некоторые из этих маркёров, такие как протеины S100 А7, А8 и А9, экспрессируются не только при псори-азе [25,33], но также в случае других воспали-тельных кожных заболеваний [16,29]. В работах M. Nold и соавт.…”

“…(2013) показана увеличенная экс-прессия IL-36γ в коже у пациентов с псориазом (n=38 и n=17) [20]. В отличие от других маркё-ров, описанных раннее при псориазе, например S100 А7, А8 и А9 [16,23,25,33], маркёр IL-36γ ока-зался высокоспецифичным для псориаза (при других воспалительных заболеваниях кожи, в том числе атопическом дерматите и контактной экземе, экспрессия выражена слабо) [20].…”

The Association between the IL-20 –1723C→G Allele on the 1q Chromosome and Psoriasis Triggered or Exacerbated by an Upper Respiratory Tract Infection in the Chinese Han Population

“…The EDC includes members of S100 and small proline-rich region (SPRR) gene clusters and cornified envelope genes known to be structurally related to SPRR or S100 genes, including filaggrin, trichohyalin, loricrin and involucrin. Among these genes, loricrin[26], S100A2 [27] and S100A7 [28] are excluded as candidates for the PSORS4 locus. A recent study revealed that the association of psoriasis to the PGLYRP and SPRR genes at the PSORS4 locus on 1q21 shows heterogeneity among Finnish, Swedish and Irish families [29].…”