Aims: 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. Patients & methods: 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. Results: Both cholestatic liver diseases were characterized by global hypomethylation, with pathway enrichment demonstrating distinct genes and pathways associated with the methylome. Conclusions: This novel study demonstrated that differential methylation in cholestatic liver disease was associated with unique pathways, suggesting it may drive disease pathogenesis.
Keywords: DNA methylation; alcoholic liver disease; alcoholic steatohepatitis; cirrhosis; differentially methylated regions; epigenetic; methylome; primary biliary cholangitis; primary biliary cirrhosis; primary sclerosing cholangitis.
While DNA is the permanent code that defines each living being, the epigenome comprises sequences attached to DNA that can change with the environment. This means that abnormal changes to the epigenome may lead to disease and that finding and treating these abnormalities may in turn help treat disease. In this study of liver tissue from individuals with two rare liver diseases, primary sclerosing cholangitis and primary biliary cholangitis, the authors found that the epigenome of these two conditions is distinct, suggesting that the epigenome is linked to the development of these conditions and may be the key to treating them.