Division of Gastroenterology, The Ottawa Hospital, Ottawa, ON, K1H 8L6, Canada.
Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
Epigenomics. 2022 Apr;14(8):481-497. doi: 10.2217/epi-2021-0343. Epub 2022 Apr 27.
In this methylome-wide association study of cholestatic liver diseases (primary sclerosing cholangitis and primary biliary cholangitis), the authors aimed to elucidate changes in methylome and pathway enrichment to identify candidate genes Reduced representation bisulfite sequencing was performed on liver tissue from 58 patients with primary sclerosing cholangitis (n = 13), primary biliary cholangitis (n = 20), alcoholic liver disease (n = 21) and live liver donors (n = 4). Pathway enrichment and network analysis were used to explore key genes/pathways. Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.
在这项关于胆汁淤积性肝病（原发性硬化性胆管炎和原发性胆汁性胆管炎）的全基因组甲基化关联研究中，作者旨在阐明甲基化组的变化和途径富集，以确定候选基因。对 58 名原发性硬化性胆管炎（n=13）、原发性胆汁性胆管炎（n=20）、酒精性肝病（n=21）和活体肝供体（n=4）患者的肝组织进行了简化代表性双硫代测序。利用途径富集和网络分析来探索关键基因/途径。这两种胆汁淤积性肝病均表现为全基因组低甲基化，途径富集显示与甲基化组相关的独特基因和途径。这项新的研究表明，胆汁淤积性肝病中的差异甲基化与独特的途径相关，提示其可能驱动疾病发病机制。
