Affiliation:
1. Zhejiang Chinese Medical University Hangzhou People's Republic of China
2. The Second Clinical Medical College of Zhejiang Chinese Medical University Hangzhou People's Republic of China
3. The Second Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou People's Republic of China
Abstract
AbstractAimSjögren syndrome (SS) is a slowly progressive, inflammatory, autoimmune disease. The aim of this study was to construct the DNA methylation profiles of whole blood of SS patients and healthy controls (HC), and to explore the role of differentially methylated genes in the pathogenesis of the disease.MethodsWhole‐genome bisulfite sequencing was performed on three SS patients and four HC. The biological function of genes associated with differentially methylated regions (DMRs) was investigated using Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis, using network‐based key driver analysis (KDA) to find KDA genes. In clinical samples of SS patients and controls, the expression levels of KDA genes were validated by quantitative real‐time polymerase chain reaction and immunohistochemical analysis. Moreover, the diagnostic value of KDA genes for SS was confirmed using receiver operating characteristic curves.ResultsWe identified 322 DMRs, annotated as 162 associated genes. Six genes were selected via the number of networks of KDA genes. Differential expression of genes such as human leukocyte antigen (HLA) class I, ADAR, and OAS2 was observed in patients' peripheral blood mononuclear cells and the minor salivary glands, which can be used as potential diagnostic biomarkers for SS.ConclusionClinical sample validation suggested that HLA class I, ADAR, and OAS2 might play a role in the development of SS. Our study shows epigenetic regulatory mechanisms and potential disease markers associated with SS, which in turn will enable us to identify new therapeutic targets.
Funder
National Natural Science Foundation of China
Cited by
1 articles.
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