Genetic Association Study of <i>TNFAIP3</i>, <i>IFIH1</i>, <i>IRF5</i> Polymorphisms with Polymyositis/Dermatomyositis in Chinese Han Population

<div><p>Background</p><p>Single-nucleotide polymorphisms (SNPs) in the <i>TNFAIP3</i>, <i>IFIH1</i>, and <i>IRF5</i> 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 <i>TNFAIP3</i>, <i>IFIH1</i>, and <i>IRF5</i> gene polymorphisms confer susceptibility for the IIMs in Chinese Han population.</p><p>Methods</p><p>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 <i>TNFAIP3</i> region (rs2230926 and rs5029939), the <i>IFIH1</i> gene (rs1990760 and rs3747517) and the <i>IRF5</i> region (rs4728142 and rs729302) were assessed and genotyped using the Sequenom MassArray iPLEX platform.</p><p>Results</p><p>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, <i>P_c</i> = 7.5×10⁻³; OR: 1.88, 95%CI: 1.30–2.74, <i>P_c</i> = 4.0×10⁻³, respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21–2.21, <i>P_c</i> = 6.0×10⁻³; OR: 1.88, 95%CI: 1.28–2.76, <i>P_c</i> = 5.5×10⁻³,respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (<i>P_c</i> = 0.04 and <i>P_c</i> = 0.016; <i>P_c</i> = 0.02 and <i>P_c</i> = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (<i>P_c</i> = 0.026 and <i>P_c</i> = 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.</p><p>Conclusions</p><p>This was the first study to reveal <i>TNFAIP3</i> and <i>IRF5</i> polymorphisms were associated with PM/DM patients or these patients with ILD, indicating that <i>TNFAIP3</i> and <i>IRF5</i> might be the susceptibility gene for PM/DM patients in Chinese Han population.</p>