| Objective:Idiopathic inflammatory myopathies (IIM) are autoimmune diseases influenced by genetic background and environmental factors. Polymyositis (PM) and dermatomyositis (DM) are the most common subtypes. Recently, FAM167A-BLK gene has been identified as a potential genetic susceptibility locus for DM in patients of European and Japanese populations. Single-nucleotide polymorphisms (SNP) in the TNFAIP3, IFIH1, and IRF5 genes have been associated with several auto-inflammation diseases, while the susceptibility between these genes and IIMs were not reported. Our aim here is to investigate the association between TNFAIP3, IFIHl, IRF5 and FAM167A-BLK genes polymorphisms and IIMs risk in Chinese Han.Methods:A large case-control study of Chinese subjects with PM (n=310) and DM (n=541) is accomplished.968 healthy and ethnically matched controls are available for comparison. Eleven SNPs in the TNFAIP3 region (rs2230926 and rs5029939), the IFIH1 gene (rs1990760 and rs3747517), the IRF5 region (rs4728142) and the FAM167A-BLK region (rs2736340, rs7812879, rsl3277113, rs2618479, rs2254546 and rs2248932) are assessed and genotyped using the Sequenom MassArray iPLEX platform.Results:Our study indicates a strong allele association is observed in DM, PM and PM/DM patients for rs2230926 (OR=1.45,95%CI= 1.04-2.03, P=0.03; OR=1.88, 95%CI=1.30-2.74, P=8.0×10-4; OR=1.61,95%CI=1.20-2.16, P=1.5×10-3, respectively) and rs5029939 (OR=1.50,95%CI=1.07-2.11, P=0.02; OR=1.88,95%CI=1.28-2.76, P=1.1×10-3; OR=1.64,95%CI=1.21-2.21, P=1.2×10-3, respectively) in the TNFAIP3 gene region, for rs4728142 (OR=1.30,95%CI=1.05-1.59, P=0.01; OR=1.30, 95%CI=1.01-1.68, P=0.04; OR=1.30,95%CI=1.08-1.56, P=5.2×10-3, respectively) in the IRF5 gene region, and for rs2736340 (OR=0.81,95%CI=0.68-0.97, P=0.02; OR=0.71, 95%CI=0.57-0.88, P=2.24×10-3; OR=0.77,95%CI=0.66-0.90, P=1.08×10-3, respectively), rs7812879 (OR=0.81,95%CI=0.67-0.98, P=0.029; OR=0.72,95%CI=0.57-0.91, P=6.74×10-3; OR=0.78,95%CI=0.66-0.92, P=2.79×10-3, respectively), rs13277113 (OR=0.81,95%CI=0.68-0.96, P=0.016; OR=0.75,95%CI=0.60-0.93, P=7.77×10-3; OR=0.79,95%CI=0.68-0.91, P=1.77×10-3, respectively), and rs2618479 (OR=0.82, 95%CI=0.69-0.99, P=0.035; OR=0.77,95%CI=0.62-0.97, P=0.023; OR=0.81, 95%CI=0.69-0.94, P=6.69×10-3, respectively) in the FAM167A-BLK gene region. In addition, TNFAIP3 rs2230926 genotype has significant association with PM and PM/DM patients (P=4.0×10-3 and P=7.7×10-3, respectively). IRF5 rs4728142 genotype has significant association with DM and PM/DM patients (P=8.4×10-3 and P=9.6×10-3, respectively). FAM167A-BLK rs2736340, rs7812879 and rs13277113 have significant association with PM and PM/DM patients (P=9.0×10-3 and P=5.3×10-3; P=0.023 and P=0.014; P=0.027 and P=8.3×10-3; respectively). Further analysis with three logistic regression genetic models reveal statistically significant difference in the TNFAIP3, IRF5 and FAM167A-BLK genotypic distributions in the DM, PM or PM/DM patients when the additive and dominant models are used. The CT haplotype (rs2230926 C-rs5029939 T) has a lower frequency between DM, PM or PM/DM patients and controls (P=9.5×10-3, P=5.0×10-4 and P=4.0×10-4, respectively). The TGCAT haplotype (rs2736340 T- rs7812879G- rsl3277113C- rs2618479A- rs2254546T) has a lower frequency between DM, PM or PM/DM patients and healthy controls(P=0.018,P=6.8x10-3 and P=2.0x10-3, Kspectively).Conclusions: Our study reveals that TNFAIP3, IRF5 and FAM167A-BLK polymorphisms are associated with DM, PM or PM/DM patients,indicating that TNFAIP3,IRF5 and FAM167A-BLK genes might be the susceptibility gene for PM/DM patients in Chinese Han population and PM/DM might share common gene with other autoimmune diseases.
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