Protein Tyrosine Phosphatase Gene PTPN22 Polymorphism in Psoriasis: Lack of Evidence for Association
Year: 2005
Type: article
Study design: Observational Study
Abstract: disease; GRR, genotype relative risk; GRR1, genotype relative risk for carriers of one copy of the test allele; GRR2, genotype relative risk for carriers of two copies of the test allele; PDT, pedigree disequilibrium test; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; SNP, single nucleotide polymorphism; T1D, type 1 diabetes; TDT, transmission/disequilibrium test LYP, the protein product of the protein tyrosine phosphatase gene PTPN22 located on human chromosome 1p13.2, is involved in downregulation of T cell signaling through its interaction with C-terminal Src tyrosine kinase (Csk) (Cloutier and Veillette, 1996), by phosphorylation of regulatory tyrosines on the Src family kinase Lck (Cloutier and Veillette, 1999). A missense mutation of this gene (C1858T, R620W), found in 15%–17 % of the Caucasian population, has been associated with autoimmune pathology in type I diabetes (T1D) (Bottini et al, 2004; Onengut-Gumuscu et al, 2004; Smyth et al, 2004; Ladner et al, 2005), rheumatoid arthritis (RA) (Begovich et al, 2004), systemic lupus erythematosus (SLE) (Kyogoku et al, 2004), and Graves disease (GD) (Smyth et al, 2004; Velaga et al, 2004) but not in multiple sclerosis (Begovich et al, 2005). It has also been shown to be functionally relevant in terms of binding to Csk (Bottini et al, 2004) and inhibition of signalling via the T cell antigen receptor (Begovich et al, 2004). Although no genome-wide search has identified human chromosome 1p13.2 as a psoriasis susceptibility locus, the widely accepted concept that psoriasis is mediated at least in part by activated T cells (Lew et al, 2004; Sugiyama et al, 2005) suggests PTPN22 as a prime target for candidate gene testing in psoriasis. In this study, we investigated association of the PTPN22 C1858T polymorphism in our collection of 517 families containing 1,146 affected individuals. This study was carried out in accordance with the Principles of Helsinki and was approved by the ethical boards of the
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W1582186754