Epigenetics and Primary Biliary Cirrhosis a Compr

Authors: YuQing Xie HongDi Ma ZheXiong Lian

Publish Date: 2015/08/13

Volume: 50, Issue: 3, Pages: 390-403

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Abstract

Primary biliary cirrhosis PBC is a chronic inflammatory autoimmune disease that develops based upon the interaction of genetic and environmental factors Recent genomewide association studies GWAS have identified dozens of predisposing variants including HLA IL12A and CTLA4 but have been disappointed in identifying a “smoking gun” These discoveries highlight the importance of the genetic background involved in immunological dysregulation Although concordance rate of PBC in monozygotic MZ twins is among the highest reported in autoimmune disorders incomplete disease concordance in twins associated with differentially expressed genes has been demonstrated However little is understood about how environmental aspects contribute to the disease and why middleaged women are more susceptible As a result epigenetic factors which convert signals indicating environmental changes into dynamic and heritable alterations of transcriptional potential are getting increased attention by researchers in both basic and clinical studies Among epigenetic mechanisms the instability and skewed gene expression in the X chromosome may account for the female preponderance in PBC In addition transcriptional regulation of histone modification and DNA methylation underscores potential involvement in disease pathogenesis Highthroughput techniques are being used to identify epigenetic regulators In this review we attempt to outline recent progress regarding epigenetics in PBC and other autoimmune diseases

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