Clinical and epidemiological research ▶ Additional supplementary tables are published online only. To view these files please visit the journal online 1 Department of Rheumatology, Tokyo Women’s Medical University, Tokyo, Japan 2 Department of Neuromuscular Research, Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan Correspondence to Yasushi Kawaguchi, Institute of Rheumatology, Tokyo Women’s Medical University, 10-22 Kawada-cho, Shinjuku-ku, Tokyo 162-0054, Japan; y-kawa@ior.twmu.ac.jp Received 28 September 2011 Accepted 31 January 2012 ABSTRACT Objectives To investigate associations between signal transducer and activator of transcription 4 (STAT4), one of the most commonly acknowledged genes for the risk of multiple autoimmune diseases, with susceptibility to adult-onset polymyositis/dermatomyositis among Japanese individuals. Methods A single nucleotide polymorphism of STAT4, rs7574865, was genotyped using TaqMan assay in 1143 Japanese individuals. The first set comprised 138 polymyositis/dermatomyositis patients and 289 controls and the second set comprised 322 patients and 394 controls. 460 patients (273 polymyositis and 187 dermatomyositis patients) and 683 controls were genotyped. Results rs7574865T conferred a risk of polymyositis/ dermatomyositis with an OR of 1.37 (95% CI 1.16 to 1.64; p=4x10 -4 ; p corr =0.0012). Both polymyositis and dermatomyositis exhibited high associations with the rs7574865T allele (polymyositis: OR=1.36, 95% CI 1.11 to 1.67; p=0.0039; p corr =0.012; dermatomyositis: OR=1.40, 95% CI 1.10 to 1.78; p=0.0054; p corr =0.016). The association between this STAT4 polymorphism and interstitial lung disease (ILD) was also investigated in the first set of polymyositis/dermatomyositis patients (n=138); those with ILD (n=79) bore rs7574865T more frequently compared with controls (OR 1.59, 95% CI 1.10 to 2.28; p=0.013; p corr =0.039). Conclusion This is the first study to show a positive association between a STAT4 polymorphism and polymyositis/dermatomyositis, suggesting that polymyositis/dermatomyositis shares a gene commonly associated with the risk of other autoimmune diseases. Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases that affect skeletal muscles. Their common clinical feature is muscle weakness, and muscle biopsies typically show inflammatory cell infiltrates. IIM are clinically sub- divided into several subgroups, including polymyo- sitis, dermatomyositis, inclusion body myositis, myositis overlapping with another connective tis- sue disease (CTD), and cancer-associated myositis. Although the pathogenesis of IIM remains unclear, some environmental factors, such as viral infec- tions, might trigger disease onset in genetically sus- ceptible individuals, as is often the case with other autoimmune diseases. Several studies have attempted to clarify the con- tributions of genetic factors for IIM susceptibility. EXTENDED REPORT Positive association between STAT4 polymorphisms and polymyositis/dermatomyositis in a Japanese population Tomoko Sugiura, 1 Yasushi Kawaguchi, 1 Kanako Goto, 2 Yukiko Hayashi, 2 Rie Tsuburaya, 2 Takefumi Furuya, 1 Takahisa Gono, 1 Ichizo Nishino, 2 Hisashi Yamanaka 1 Among possible candidate genes, major histocom- patibility complex (human leucocyte antigen (HLA)) genes have been investigated most frequently. 1 In North American Caucasian patients, HLA alleles of the 8.1 ancestral haplotype (particularly HLA- B*0801 and DRB1*0301) are the principal HLA risk loci. 2 Among Japanese, HLA-DRB1*0803 was found to be associated with IIM and anti-amino- acyl-tRNA synthetase antibody. 3 Several genes outside the HLA regions, including the proinflam- matory cytokines tumour necrosis factor alpha, interleukin (IL)-1α, IL-1β and interferon (IFN) γ, and an immunoglobulin gene 4–7 were found to be associated with specific IIM subgroups, particularly juvenile dermatomyositis. However, because these diseases are rare and there is a broad spectrum of disease entities, genetic risk fac- tors for IIM have not been thoroughly investigated. A functional variant of the protein tyrosine phosphatase N22 gene (PTPN22), an R620W polymorphism, was recently found to be associated with adult and juve- nile IIM in British Caucasian patients. 8 This suggested that IIM might share a common genetic background with other autoimmune diseases. Most susceptibility genes common to autoimmune diseases were originally identified in systemic lupus erythematosus (SLE) patients using genome-wide association studies. Among these, the following genes contributed most prominently: IFN regula- tory factor 5 (IRF5), signal transducer and activator of transcription 4 (STAT4), PTPN22, B-lymphoid tyrosine kinase (BLK), B-cell scaffold protein with ankyrin repeats (BANK1) and tumour necrosis factor alpha-induced protein 3 (TNFAIP3). Their involve- ment has been replicated in different ethnic groups. 9 Furthermore, these genes were also found to be asso- ciated with the risk of several other autoimmune dis- eases including rheumatoid arthritis (RA), 10 systemic sclerosis (SSc), 11 12 and type I diabetes mellitus. 13 The present study is the first to investigate the possible involvement of STAT4, the best established gene for susceptibility to autoimmune diseases across different ethnic groups, in the susceptibil- ity to adult-onset polymyositis/dermatomyositis among Japanese individuals. METHODS Subjects We enrolled polymyositis or dermatomyositis patients who were 18 years or older at disease onset and who had probable or definite myositis based on 1646 Ann Rheum Dis 2012;71:1646–1650. doi:10.1136/annrheumdis-2011-200839 annrheumdis-2011-200839) (http://dx.doi.org/10.1336/ group.bmj.com on December 17, 2012 - Published by ard.bmj.com Downloaded from