title: 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: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Manchester Rheumatic Diseases Centre, Hope Hospital, Salford, UK.
authors.forename: H
authors.initials: H
authors.lastname: Chinoy
authors.forename: H
authors.initials: H
authors.lastname: Platt
authors.forename: J A
authors.initials: JA
authors.lastname: Lamb
authors.forename: Z
authors.initials: Z
authors.lastname: Betteridge
authors.forename: H
authors.initials: H
authors.lastname: Gunawardena
authors.forename: N
authors.initials: N
authors.lastname: Fertig
authors.forename: H
authors.initials: H
authors.lastname: Varsani
authors.forename: J
authors.initials: J
authors.lastname: Davidson
authors.forename: C V
authors.initials: CV
authors.lastname: Oddis
authors.forename: N J
authors.initials: NJ
authors.lastname: McHugh
authors.forename: L R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: W E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: R G
authors.initials: RG
authors.lastname: Cooper
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D009220:Myositis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D006113:United Kingdom; D044465:White People
chemical_list: D001323:Autoantibodies; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22