%0 Journal Article
%T Association of functional variants of PTPN22 and tp53 in psoriatic arthritis: a case-control study
%A Christopher Butt
%A Lynette Peddle
%A Celia Greenwood
%A Sean Hamilton
%A Dafna Gladman
%A Proton Rahman
%J Arthritis Research & Therapy
%D 2005
%I BioMed Central
%R 10.1186/ar1880
%X Recently, two novel genes have attracted attention in the investigation of autoimmune disease. The PTPN22 gene encodes a functional protein tyrosine phosphatase known as lymphoid phosphatase, which acts as a regulator of the negative regulatory kinase cytoplasmic tyrosine kinase in T cells, and may play a role in suppressing T cell activation [1]. A functional single nucleotide polymorphism (SNP) at nucleotide position 1858, causing an Arg¡úTrp substitution (R620W) that disrupts the binding site for cytoplasmic tyrosine kinase, was recently found to be associated with type 1 (insulin dependent) diabetes [2]. Subsequently, associations were also found with other autoimmune diseases, including rheumatoid arthritis (RA) [3] and systemic lupus erythematosus [4] in Caucasian populations. A large study in psoriasis involving 1,146 affected individuals [5] and a smaller study in psoriasis in 265 families with multiple autoimmune diseases [6], with only 63 psoriatics, revealed no association of the R620W variant of PTPN22 with psoriasis.The p53 protein has long been known to be related to the regulation of cell growth and prevention of carcinogenesis. It was recently shown that tp53 is consistently underexpressed in several autoimmune diseases, including RA, systemic lupus erythematosus, multiple sclerosis and type 1 diabetes [7]. Furthermore, the cellular damage response pathways that are dependent on p53 are defective in patients with RA [8]. A functional variant of p53 (Pro72Arg) has been shown to induce apoptosis markedly better than the wild-type variant, and has been associated juvenile chronic arthritis [9] but not with adult-onset RA [10].Although psoriasis and psoriatic arthritis (PsA) are interrelated disorders, PsA is a distinct entity with its own epidemiological, clinical and genetic features. Furthermore, PsA exhibits much greater heritability among first-degree relatives (¦Ë1 48) than does psoriasis (¦Ë1 5¨C10) [11]. Therefore, we set out to examine the associati
%U http://arthritis-research.com/content/8/1/R27