Genetic association study of TNFAIP3, IFIH1, IRF5 polymorphisms with polymyositis/dermatomyositis in Chinese Han population

PLoS One. 2014 Oct 22;9(10):e110044. doi: 10.1371/journal.pone.0110044. eCollection 2014.

Abstract

Background: Single-nucleotide polymorphisms (SNPs) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and idiopathic inflammatory myopathies (IIMs) were not reported. This study aimed to investigate whether TNFAIP3, IFIH1, and IRF5 gene polymorphisms confer susceptibility for the IIMs in Chinese Han population.

Methods: A large case-control study of Chinese subjects with polymyositis (PM) (n = 298) and dermatomyositis (DM) (n = 530) was accomplished. 968 healthy and ethnically matched controls were available for comparison. Six SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517) and the IRF5 region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform.

Results: Our study indicated a strong allele association was observed in PM/DM and PM patients for rs2230926 (OR: 1.61, 95%CI: 1.20-2.16, P(c) = 7.5×10(-3); OR: 1.88, 95%CI: 1.30-2.74, P(c) = 4.0×10(-3), respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21-2.21, P(c) = 6.0×10(-3); OR: 1.88, 95%CI: 1.28-2.76, P(c) = 5.5×10(-3), respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (P(c) = 0.04 and P(c) = 0.016; P(c) = 0.02 and P(c) = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (P(c) = 0.026 and P(c) = 0.048, respectively). Further analysis with three logistic regression genetic models revealed statistically significant difference in the genotypic distribution in the PM/DM, PM or DM patients when the additive and dominant models were used.

Conclusions: This was the first study to reveal TNFAIP3 and IRF5 polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that TNFAIP3 and IRF5 might be the susceptibility gene for PM/DM patients in Chinese Han population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Asian People
  • Case-Control Studies
  • DEAD-box RNA Helicases / genetics
  • DNA-Binding Proteins / genetics*
  • Dermatomyositis / complications
  • Dermatomyositis / ethnology
  • Dermatomyositis / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • Humans
  • Interferon Regulatory Factors / genetics*
  • Interferon-Induced Helicase, IFIH1
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Logistic Models
  • Lung Diseases, Interstitial / complications
  • Lung Diseases, Interstitial / ethnology
  • Lung Diseases, Interstitial / genetics*
  • Male
  • Middle Aged
  • Models, Genetic
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Polymyositis / complications
  • Polymyositis / ethnology
  • Polymyositis / genetics*
  • Tumor Necrosis Factor alpha-Induced Protein 3

Substances

  • DNA-Binding Proteins
  • IRF5 protein, human
  • Interferon Regulatory Factors
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • IFIH1 protein, human
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1

Grants and funding

This work was supported by funding from the Research Special Fund for Public Welfare Industry of Health (201202004), and the National Natural Science Foundation of China Grants (81172857, 81373188), the Chinese National High Technology Research and Development Program, Ministry of Science and Technology Grants (2011AA02A113), and the National Science Technology Pillar Program in the 12nd Five-year Plan (2014BAI07B00). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.