Association between a C8orf13-BLK polymorphism and polymyositis/dermatomyositis in the Japanese population: an additive effect with STAT4 on disease susceptibility

PLoS One. 2014 Mar 14;9(3):e90019. doi: 10.1371/journal.pone.0090019. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian Continental Ancestry Group / genetics
  • Dermatomyositis / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Polymyositis / genetics*
  • Proteins / genetics*
  • Proteins / metabolism
  • STAT4 Transcription Factor / genetics*
  • STAT4 Transcription Factor / metabolism

Substances

  • FAM167A protein, human
  • Proteins
  • STAT4 Transcription Factor

Grant support

This study was supported by autoimmune disease research grants from the Ministry of Health, Labor, and Welfare, Japan and was partly supported by an Intramural Research Grant (23-4, 23-5) for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.