PTPN22 haplotype associations in UK Caucasian patients with adult and juvenile onset idiopathic inflammatory myopathy (IIM)

Purpose: We have previously demonstrated an association of the single nucleotide polymorphism (SNP) (rs2476601, 1858C→T, R620W) in the protein tyrosine phosphatase N22 (PTPN22) gene with adult and juvenile UK Caucasian IIM (Chinoy et al, Rheumatology 2008;47 supp 2:ii13). The aim of this study was to examine whether further PTPN22 SNPs conferred disease susceptibility and formed haplotypes in IIM. Methods: Data from 408 IIM cases (300 adult, 49±14.0 years, 72% female; 108 juvenile, 6±3.6 years 73% female), recruited from the UK Adult Onset Myositis Immunogenetic Collaboration and the Juvenile Dermatomyositis (JDM) National Registry and Repository, were compared to 735 randomly selected Caucasian controls. IIM was confirmed as probable/definite (Bohan & Peter, 1975) and stratified by disease subtype (polymyositis [PM], dermatomyositis [DM], myositis/connective tissue disease [CTD]-overlap, JDM). DNA was genotyped using Sequenom iPlex™. Seventeen SNPs were selected: 3 SNPs were removed due to an assay success rate 5% (see Table). The most frequent control haplotype corresponded to that seen in a previous RA study (Carlton et al, 2005). Only one haplotype carried the R620W T allele (CAGATTCT). This haplotype was significantly associated with IIM combined, PM and JDM vs. controls. The CGAGCCTT haplotype was a protective factor in JDM vs. controls. Haplotype frequencies were re-analysed in the absence of the R620W risk T allele; no further significant associations were observed. Conclusions: No associations are present in PTPN22 SNPs independent of the R620W variant in UK Caucasian IIM.