Genetic polymorphisms in the cell growth regulated gene, SC1 telomeric of the HLA‐C gene and lack of association of psoriasis vulgaris

Abstract

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. We have previously narrowed down the critical region most likely to contain the psoriasis vulgaris gene to 111 kb spanning 89 kb to 200 kb telomeric of the HLA-C locus by microsatellite mapping. This segment includes three known genes (POU5F1, SC1 and S) and four new expressed genes. Among them, SC1 (TCF19) is the cell growth regulated gene possibly with trans-activator activity. Since psoriasis vulgaris is a common skin disorder characterized by hyperproliferation of epidermal cells, it is tempting to speculate that the SCI gene is one of the strong candidate genes responsible for the development of psoriasis vulgaris. Here, we investigated genetic polymorphisms in the SC1 gene by direct DNA sequencing and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques. Three single nucleotide polymorphisms in exon 2, two of which are accompanied by amino-acid substitutions, were identified. Further, one 4-bp deletion polymorphism was detected around the acceptor site of the lariat-shaped structure necessary for RNA splicing in intron 2. No significant difference in the dimorphic or haplotypic distribution at these four polymorphic sites was observed between the patients with psoriasis vulgaris and healthy controls. This suggests that the susceptible gene for psoriasis vulgaris is not the SC1 gene itself, although a unique homozygous haplotype was identified in the patients.

A whole-genome association study of major determinants for allopurinol-related Stevens–Johnson syndrome and toxic epidermal necrolysis in Japanese patients

“…[20][21][22][23] TCF19 is a potential trans-activating factor that could play an important role in the transcription of genes required for the later stages of cell cycle progression. 27 Possible psoriasis candidate genes near HLA-B include PSORS1C1, [17][18][19] CCHCR1, 22,23 and POU5F1. 32,33 Mutations in BAT1 may be associated with rheumatoid arthritis.…”

“…HCP5 (HLA complex P5), which is involved in hypersensitivity to abacavir, 24-26 had three SNPs (rs3094011, rs3099844 and rs31431643). TCF19 (transcription factor 19), which is a potential trans-activating factor that might play an important role in the transcription of genes required for the later stages of cell cycle progression, 27 contained two SNPs (rs9263794 and rs10448701). Two SNPs (rs9263796 and rs9263800) were also found in POU5F1 (POU class 5 homeobox; alternative names for Oct4).…”

Distinct HLA-C/KIR Genotype Profile Associates with Guttate Psoriasis

“…This region is thought to harbor a major psoriasis gene(s) and has been thoroughly investigated (Balendran et al, 1999;Oka et al, 1999;Nair et al, 2000). Several PSORS1 candidate genes were proposed and tested in association studies (STG, CDSN, PSORS1C1-3, HCR, TCF19, POU5F1, HLA-C) (Jenisch et al, 1999;Enerback et al, 2000;Gonzalez et al, 2000;Teraoka et al, 2000;O'Brien et al, 2001;Asumalahti et al, 2002;Chang et al, 2003;Holm et al, 2003;Sanchez et al, 2004;Carlen et al, 2005). The earliest association reported in psoriasis for any of these candidate genes was to HLA-C (McMichael et al, 1978).…”

Genome-wide studies of psoriasis susceptibility loci: a review

“…This interval contains several gene candidates including corneodesmosin (CDSN) [48][49][50] and Pg8/helix coiled coil rod homolog (HCR) [51], which show a strong association with psoriasis. Conversely, TCF19, which is approximately 5 kb centromeric to Pg8/HCR, failed to show any association with psoriasis [52]. Three other genes are located within the candidate region (telomeric to HCR), small proline rich (SPR1) and SEEK1 located between the CDSN and HCR and STG 2.5 kb telomeric to the CDSN [45].…”