title: Association between a C8orf13-BLK polymorphism and polymyositis/dermatomyositis in the Japanese population: an additive effect with STAT4 on disease susceptibility.
abstract: BACKGROUND
  Accumulating evidence has shown that several non-HLA genes are involved in the susceptibility to polymyositis/dermatomyositis. This study aimed to investigate the involvement of C8orf13-BLK, one of the strongest candidate genes for autoimmune diseases, in susceptibility to polymyositis/dermatomyositis in the Japanese population. A possible gene-gene interaction between C8orf13-BLK and STAT4, which we recently showed to be associated with Japanese polymyositis/dermatomyositis, was also analyzed.
  
  
  METHODS
  A single-nucleotide polymorphism in C8orf13-BLK (dbSNP ID: rs13277113) was investigated in the Japanese population using a TaqMan assay in 283 polymyositis patients, 194 dermatomyositis patients, and 656 control subjects.
  
  
  RESULTS
  The C8orf13-BLK rs13277113A allele was associated with overall polymyositis/dermatomyositis (P<0.001, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.19-1.73), as well as polymyositis (P = 0.011, OR 1.32, 95% CI 1.06-1.64) and dermatomyositis (P<0.001, OR 1.64, 95% CI 1.26-2.12). No association was observed between the C8orf13-BLK rs13277113A allele and either interstitial lung disease or anti-Jo-1 antibody positivity. The C8orf13-BLK rs13277113 A and STAT4 rs7574865 T alleles had an additive effect on polymyositis/dermatomyositis susceptibility. The strongest association was observed in dermatomyositis, with an OR of 3.07 (95% CI; 1.57-6.02) for the carriers of four risk alleles at the two SNP sites, namely, rs1327713 and rs7574865.
  
  
  CONCLUSIONS
  This study established C8orf13-BLK as a new genetic susceptibility factor for polymyositis/dermatomyositis. Both C8orf13-BLK and STAT4 exert additive effects on disease susceptibility. These observations suggested that C8orf13-BLK, in combination with STAT4, plays a pivotal role in creating genetic susceptibility to polymyositis/dermatomyositis in Japanese individuals.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sugiura
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, and Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, and Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Gono
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Furuya
authors.affiliation: Department of Neuromuscular Research, National Institute of Neuroscience, and Department of Clinical Development, Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D003882:Dermatomyositis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017285:Polymyositis / Q000235:genetics*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D064267:Intrinsically Disordered Proteins
chemical_list: D011506:Proteins; D050797:STAT4 Transcription Factor; C584607:FAM167A protein, human; D064267:Intrinsically Disordered Proteins