PMID- 37740638 OWN - NLM STAT- MEDLINE DCOM- 20231102 LR - 20231102 IS - 1756-185X (Electronic) IS - 1756-1841 (Linking) VI - 26 IP - 11 DP - 2023 Nov TI - Genome-wide DNA methylation sequencing reveals epigenetic features and potential biomarkers of Sjogren syndrome. PG - 2223-2232 LID - 10.1111/1756-185X.14918 [doi] AB - AIM: Sjogren 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. METHODS: Whole-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. RESULTS: We 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. CONCLUSION: Clinical 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. CI - (c) 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd. FAU - Lu, Ding-Qi AU - Lu DQ AUID- ORCID: 0000-0003-4503-8486 AD - Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Yao, Xin-Yi AU - Yao XY AUID- ORCID: 0000-0002-7371-0885 AD - The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Ren, Ya-Ting AU - Ren YT AD - The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Zhang, Kai-Yuan AU - Zhang KY AD - The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Zhu, Xin-Chao AU - Zhu XC AD - The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Hong, Tao AU - Hong T AD - The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Yu, Xue AU - Yu X AD - The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Xie, Zhi-Min AU - Xie ZM AD - The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Chen, Li-Ying AU - Chen LY AD - The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. FAU - Wang, Xin-Chang AU - Wang XC AUID- ORCID: 0000-0002-4540-301X AD - The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People's Republic of China. LA - eng GR - Y202248715/General Research Project of Education Department of Zhejiang Province/ GR - 82074341/National Natural Science Foundation of China/ PT - Journal Article DEP - 20230923 PL - England TA - Int J Rheum Dis JT - International journal of rheumatic diseases JID - 101474930 RN - 0 (Biomarkers) SB - IM MH - Humans MH - *DNA Methylation MH - *Sjogren's Syndrome/diagnosis/genetics MH - Leukocytes, Mononuclear MH - Epigenesis, Genetic MH - Biomarkers OTO - NOTNLM OT - DNA methylation OT - Sjogren syndrome OT - diagnostic markers OT - epigenetics OT - whole-genome bisulfite sequencing EDAT- 2023/09/23 11:43 MHDA- 2023/11/02 12:45 CRDT- 2023/09/23 05:27 PHST- 2023/08/08 00:00 [revised] PHST- 2023/02/07 00:00 [received] PHST- 2023/09/03 00:00 [accepted] PHST- 2023/11/02 12:45 [medline] PHST- 2023/09/23 11:43 [pubmed] PHST- 2023/09/23 05:27 [entrez] AID - 10.1111/1756-185X.14918 [doi] PST - ppublish SO - Int J Rheum Dis. 2023 Nov;26(11):2223-2232. doi: 10.1111/1756-185X.14918. Epub 2023 Sep 23.