单位：[1]Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China[2]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences (CAS), Beijing, China[3]Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China[4]Alpert Medical School of Brown University, Providence, Rhode Island[5]Joint Laboratory for Translational Medicine Research, Beijing Institute of Genomics, Chinese Academy of Sciences & Liaocheng People's Hospital, Liaocheng, China
Objectives: Previous association studies have identified genetic variants in the human leukocyte antigen (HLA) complex as substantial risk factors for idiopathic inflammatory myopathies (Ms). However, a great number of genes are located in the HLA region, and thus fine mapping is quite necessary. Methods: Targeted capture sequencing were performed on the whole HLA region in 42 IIM patients and 24 healthy controls. A microarray analysis was applied to analyze gene expression profiles in additional 20 newly diagnosed IIM and five healthy controls. Results: The HLA region was confirmed to be associated with IIMs in Chinese patients. By gene expression profiling and pathway analysis, several genes were identified as candidates for IIM risk factors, including HLA-A, HLA-B, HLA-DRB5, HLA-DRB1, HLA-DQA1, HLA-DQB1 and HLA-DQB2. Interestingly, p.Y107V of the HLA-DRB1 was predicted to be a potential causal non-synonymous variation for IIMs that may affect the antigen-binding groove of the HLA-II molecule. Conclusions: Our data have revealed novel genetic variations in the HLA region of IIM patients and provide new insight into the pathogenesis and diagnosis of IIMs.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [91542121, 81571603, 81701615]; Capital Foundation of Medical Developments [2016-2-4063]; Beijing Municipal Science & Technology CommissionBeijing Municipal Science & Technology Commission [Z181100001718063]
第一作者单位：[1]Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China[2]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences (CAS), Beijing, China[5]Joint Laboratory for Translational Medicine Research, Beijing Institute of Genomics, Chinese Academy of Sciences & Liaocheng People's Hospital, Liaocheng, China[*1]Department of Rheumatology, China-Japan Friendship Hospital, No. 2 Yinghua East Road, Chaoyang District, Beijing 100029, China[*2]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, No. 1 Beichen West Road, Chaoyang District, Beijing 100101, China
推荐引用方式(GB/T 7714)：
Peng Qing-Lin,Lin Jin-Ming,Zhang Yong-Biao,et al.Targeted capture sequencing identifies novel genetic variations in Chinese patients with idiopathic inflammatory myopathies[J].INTERNATIONAL JOURNAL of RHEUMATIC DISEASES.2018,21(8):1619-1626.doi:10.1111/1756-185X.13350.
APA：
Peng, Qing-Lin,Lin, Jin-Ming,Zhang, Yong-Biao,Zhang, Xue-Zhi,Wang, Pan-Pan...&Wang, Guo-Chun.(2018).Targeted capture sequencing identifies novel genetic variations in Chinese patients with idiopathic inflammatory myopathies.INTERNATIONAL JOURNAL of RHEUMATIC DISEASES,21,(8)
MLA：
Peng, Qing-Lin,et al."Targeted capture sequencing identifies novel genetic variations in Chinese patients with idiopathic inflammatory myopathies".INTERNATIONAL JOURNAL of RHEUMATIC DISEASES 21..8(2018):1619-1626
