Dataset Information

The protein tyrosine phosphatase N22 gene is associated with juvenile and adult idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British Caucasian patients.

ABSTRACT: To examine single-nucleotide polymorphisms (SNPs) of the protein tyrosine phosphatase N22 gene (PTPN22) and to study the relationship between PTPN22 and the HLA region in patients with idiopathic inflammatory myopathies (IIMs).PTPN22 SNPs were assessed in a large, cross-sectional, case-control study from the UK involving patients with adult or juvenile IIM, comprising patients with polymyositis (PM) (n=114), dermatomyositis (DM) (n=102), myositis associated with another connective tissue disease (myositis-CTD overlap syndrome) (n=64), or juvenile DM (n=101), in comparison with 748 control subjects. Seventeen PTPN22 SNPs were genotyped using the Sequenom MassArray iPLEX platform. Serotyping for myositis-specific/myositis-associated autoantibodies (MSAs/MAAs) was performed by radioimmunoprecipitation.A significant association was noted between the R620W variant (rs2476601) and IIM (corrected P [Pcorr]=0.0009 versus controls), and specifically with the clinical subgroup of PM (Pcorr=0.003 versus controls). A weaker association was noted with juvenile DM (Pcorr=0.009 versus controls). No significant associations were noted after stratification by serologic subgroups. The association with the R620W variant was independent of alleles forming the HLA 8.1 haplotype. No other PTPN22 SNPs were associated with IIM. The PTPN22 haplotype containing the R620W T allele was the only haplotype significantly associated with IIM.The R620W variant is a significant risk factor for IIM, independent of the HLA 8.1 haplotype. Unlike that in the HLA region, risk is not increased in individuals possessing MSAs/MAAs. These results are further evidence that the PTPN22 gene confers autoimmune susceptibility.

SUBMITTER: Chinoy H

PROVIDER: S-EPMC4568569 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The protein tyrosine phosphatase N22 gene is associated with juvenile and adult idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British Caucasian patients.

Chinoy H H Platt H H Lamb J A JA Betteridge Z Z Gunawardena H H Fertig N N Varsani H H Davidson J J Oddis C V CV McHugh N J NJ Wedderburn L R LR Ollier W E R WE Cooper R G RG

Arthritis and rheumatism 20081001 10

<h4>Objective</h4>To examine single-nucleotide polymorphisms (SNPs) of the protein tyrosine phosphatase N22 gene (PTPN22) and to study the relationship between PTPN22 and the HLA region in patients with idiopathic inflammatory myopathies (IIMs).<h4>Methods</h4>PTPN22 SNPs were assessed in a large, cross-sectional, case-control study from the UK involving patients with adult or juvenile IIM, comprising patients with polymyositis (PM) (n=114), dermatomyositis (DM) (n=102), myositis associated with ...[more]

PMID: 18821667

Similar Datasets

Project description:The aim of this study was to quantitate risk and to examine heterogeneity for HLA at high resolution in patients with the most common subtypes of juvenile idiopathic arthritis (JIA), IgM rheumatoid factor-negative polyarticular JIA and oligoarticular JIA. Use of 4-digit comprehensive HLA typing enabled great precision, and a large cohort allowed for consideration of both age at disease onset and disease subtype.Polymerase chain reaction-based high-resolution HLA typing for class I and class II loci was accomplished for 820 patients with JIA and 273 control subjects. Specific HLA epitopes, potential interactions of alleles at specific loci and between loci (accounting for linkage disequilibrium and haplotypic associations), and an assessment of the current International League of Associations for Rheumatology classification criteria were considered.An HLA-DRB1/DQB1 effect was shown to be exclusively attributable to DRB1 and was similar between patients with oligoarticular JIA and a younger subgroup of patients with polyarticular JIA. Furthermore, patients with polyarticular JIA showed age-specific related effects, with disease susceptibility in the group older than age 6 years limited to an effect of the HLA-DRB1*08 haplotype, which is markedly different from the additional susceptibility haplotypes, HLA-DRB1*1103/1104, found in the group with oligoarticular JIA and the group of younger patients with polyarticular JIA. Also in contrast to findings for oligoarticular JIA, patients with polyarticular arthritis had no evidence of an HLA class I effect. Markers associated with a reduced risk of disease included DRB1*1501, DRB1*0401, and DRB1*0701. DRB1*1501 was shown to reduce risk across the whole cohort, whereas DRB1*0401 and DRB1*0701 were protective for selected JIA subtypes. Surprisingly, the disease predisposition mediated by DPB1*0201 in individuals without any disease-predisposing DRB1 alleles was great enough to overcome even the very strong protective effect observed for DRB1*1501.Inherited HLA factors in JIA show similarities overall as well as differences between JIA subtypes.

Dataset Information

The protein tyrosine phosphatase N22 gene is associated with juvenile and adult idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British Caucasian patients.

Publications

The protein tyrosine phosphatase N22 gene is associated with juvenile and adult idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype in British Caucasian patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets