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Targeted capture sequencing identifies novel genetic variations in Chinese patients with idiopathic inflammatory myopathies
Author(s) -
Peng QingLin,
Lin JinMing,
Zhang YongBiao,
Zhang XueZhi,
Wang PanPan,
Wu TingTing,
Yu Jun,
Dong XiaoQun,
Gu MingLiang,
Wang GuoChun
Publication year - 2018
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.13350
Subject(s) - human leukocyte antigen , medicine , pathogenesis , gene , immunology , genetics , antigen , biology
Objectives Previous association studies have identified genetic variants in the human leukocyte antigen ( HLA ) complex as substantial risk factors for idiopathic inflammatory myopathies ( IIM s). 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 IIM s 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 ‐ DRB 5 , HLA ‐ DRB 1 , HLA ‐ DQA 1 , HLA ‐ DQB 1 and HLA ‐ DQB 2 . Interestingly, p.Y107V of the HLA ‐ DRB 1 was predicted to be a potential causal non‐synonymous variation for IIM s 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 IIM s.