Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with non-suppurative destruction of the intrahepatic bile ducts. The interplay of genetics and environmental triggers contributes to the onset of the disease and subsequently results in cholestasis and progressive fibrosis. Recently, genome-wide association studies (GWAS) have identified multiple genes influencing the susceptibility to PBC in HLA and non-HLA loci. However, it is estimated that the known risk variants merely account for no more than 20% of the heritability of PBC and causes of the remaining heritability remain uncertain. Increasing evidence suggests that the presence of epigenetic abnormalities may explain the "missing heritability" that cannot be captured by GWAS. Among these epigenetic mechanisms, DNA methylation, histone modification, and noncoding RNAs (i.e. miRNA and lncRNA) are involved in the pathogenesis of PBC. Additionally, telomere dysregulation in biliary epithelial cells (BECs) may play a role in disease onset, whereas a deficiency in sex chromosome and skewed gene expression in the X chromosome may to some extent explain the female dominance in PBC.
Keywords: DNA methylation; Epigenetic; Histone modification; Noncoding RNAs; Primary Biliary Cholangitis.