Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity.
Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that develops based upon the interaction of genetic and environmental factors. Recent genome-wide 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 middle-aged 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. High-throughput 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.
Liver Immunology Laboratory, Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, 230026,, China.
Yu-Qing
YQ
Xie
Liver Immunology Laboratory, Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, 230026,, China. mahongdi@ustc.edu.cn.
Hong-Di
HD
Ma
Liver Immunology Laboratory, Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui, 230026,, China. zxlian1@ustc.edu.cn.|Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, 230026,, China. zxlian1@ustc.edu.cn.
Zhe-Xiong
ZX
Lian
D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006657:Histones / Q000378:metabolism; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics; D049951:X Chromosome Inactivation
D006657:Histones; D035683:MicroRNAs; D062085:RNA, Long Noncoding
DNA methylation; Epigenetics; Histone modification; Long noncoding RNA; MicroRNA; Primary biliary cirrhosis