InUK Caucasian adult and juvenile onset idiopathic inflammatory myopathy (IIM), the PTPN22 1858 -> T polymorphism confers disease susceptibility independent of HLA-DRB1*03

Background: To examine the missense single nucleotide polymorphism (SNP) (1858C→T, rs2476601) in the protein tyrosine phosphatase N22 (PTPN22) gene in UK Caucasian IIM patients.Methods: 381 IIM cases (280 adult, 49±14.0 years; 101 juvenile, 6±3.6 years; 73% female) from the Adult Onset Myositis Immunogenetic Collaboration and the Juvenile Dermatomyositis (JDM) National Registry and Repository, were compared to 735 controls. Myositis was probable/definite as per Bohan & Peter (1975). DNA were genotyped for rs2476601 (Sequenom iPlex) and HLA-DRB1 (Dynal RELI SSO). Serotyping used radio-immunoprecipitation. Data were stratified by clinical subtype (polymyositis [PM], dermatomyositis [DM], myositis/overlap, JDM), serotype (anti-Jo-1, PL-7, PL-12, EJ, OJ, KS, Mi-2, SRP, U1-RNP, Ku, PM-Scl, 155/140 and small ubiquitin-like modifier 1 activating enzyme [SAE]), interstitial lung disease (ILD) and cancer-associated myositis (CAM).Results: Strong and significant PTPN22*T allele associations were observed in overall IIM and PM vs. controls (see table). Weaker associations were found in JDM, ILD, Jo-1 and 155/140 subgroups. No associations were noted in other antibody subgroups or CAM. The relationship between PTPN22*T and HLA-DRB1*03 (a known IIM risk factor) was assessed by logistic regression. Both PTPN22*T (odds ratio [OR] 1.7, 95% confidence interval 1.2-2.2, p=0.001) and DRB1*03 (OR 2.5, 2.0-3.3, p