Association of functional variants of PTPN22 and tp53 in psoriatic arthritis: a case-control study

Christopher Butt,Sean Hamilton,Lynette Peddle,Celia Greenwood,Dafna Gladman,Proton Rahman

doi:10.1186/ar1880

Abstract

Recent studies have implicated PTPN22 and tp53 in susceptibility to several autoimmune diseases, including rheumatoid arthritis, suggesting that these genes are important in maintaining immune homeostasis. Because autoimmune diseases may share similar susceptibility loci, investigation of these genes in psoriatic arthritis (PsA) is of potential relevance. As a result we investigated known coding polymorphisms in PTPN22 and tp53 in a homogenous Caucasian PsA cohort from Newfoundland, Canada and an admixed Caucasian PsA cohort from Toronto, Canada. We observed a moderate association of the R620W variant of PTPN22 with PsA in the Toronto population only. Because of the conflicting findings reported regarding the association of PTPN22 with PsA, further studies in other PsA populations are warranted.

Highlights

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]
Because the Toronto cohort is the first population to report a significant association between PTPN22 and psoriatic arthritis (PsA) and contradicts previous larger studies in psoriasis [5,6], this result should be interpreted with caution until it is independently validated in another PsA population

Summary

Introduction

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→Trp substitution (R620W) that disrupts the binding site for cytoplasmic tyrosine kinase, was recently found to be associated with type 1 (insulin dependent) diabetes [2]. Associations were found with other autoimmune diseases, including rheumatoid arthritis (RA) [3] and systemic lupus erythematosus [4] in Caucasian populations. It was recently shown that tp is consistently underexpressed in several autoimmune diseases, including RA, systemic lupus erythematosus, multiple sclerosis and type 1 diabetes [7]. 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]

Methods

Results

Conclusion