Abstract
BackgroundSingle-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.MethodsA 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.ResultsOur 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, Pc = 7.5×10−3; OR: 1.88, 95%CI: 1.30–2.74, Pc = 4.0×10−3, respectively) and rs5029939 (OR: 1.64, 95%CI: 1.21–2.21, Pc = 6.0×10−3; OR: 1.88, 95%CI: 1.28–2.76, Pc = 5.5×10−3,respectively). And rs2230926 and rs5029939 were significantly associated with interstitial lung disease (ILD) in PM/DM and PM patients (Pc = 0.04 and Pc = 0.016; Pc = 0.02 and Pc = 0.03, respectively). In addition, rs4728142 allele and genotype had significant association with PM/DM patients (Pc = 0.026 and Pc = 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.ConclusionsThis 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.
Highlights
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare systemic disease characterized by skeletal muscle weakness and presented with extra-muscular manifestations such as skin rashes, interstitial lung disease (ILD) and malignancy [1]
This study showed phospholipase C–like 1 (PLCL1) gene, B lymphoid tyrosine kinase (BLK) gene, and chemokine (C-C motif) ligand 21 (CCL21) gene were associated with DM risk
Myasthenia syndrome, muscular dystrophy, inherited, metabolic, or infectious myopathies or muscle diseases caused by other factors were systematically excluded. 968 ethnically matched healthy controls from the Peking Union Medical College Hospital were recruited during their physical examinations according to the following rules: 1) no significant history of rheumatologic disease; 2) no family history of rheumatologic diseases; 3) normal biochemical and immunological profiles; and 4) negative serology for anti-Jo-1 and anti-Mi-2 antibodies
Summary
The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of rare systemic disease characterized by skeletal muscle weakness and presented with extra-muscular manifestations such as skin rashes, interstitial lung disease (ILD) and malignancy [1]. Myositis patients may develop additional rheumatic diseases, and the occurrence of autoimmune disorders in near relatives is higher [2,3]. According to the understanding of other autoimmune diseases, it is supposed that IIMs development may be a result of both genetic and environmental factors or their interactions. It is possible to make use of the extensive knowledge of other rheumatic diseases that share pathogenic traits with IIMs to obtain insight into the probable genetic intricacy of IIMs. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
