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Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity

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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 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.

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Abbreviations

PBC:

Primary biliary cirrhosis

GWAS:

Genome-wide association study

MZ:

Monozygotic

PDC-E2:

The E2 component of pyruvate dehydrogenase complex

BEC:

Biliary epithelial cell

UDAC:

Ursodeoxycholic acid

AIH:

Autoimmune hepatitis

PSC:

Primary sclerosing cholangitis

DZ:

Dizygotic

SNP:

Single-nucleotide polymorphism

SLE:

Systemic lupus erythematosus

RA:

Rheumatoid arthritis

T1D:

Type 1 diabetes

MS:

Multiple sclerosis

PBMC:

Peripheral blood mononuclear cells

XCI:

X chromosome inactivation

Xic:

X-chromosome-inactivation center

Xist:

X inactivation-specific transcript

HAT:

Histone acetyl transferase

HDAC:

Histone deacetylase

HDACI:

Histone deacetylase inhibitors

TSS:

Transcription start site

miRNA:

MicroRNA

UTR:

Untranslated region

MRE:

miRNA recognition element

lncRNA:

Long noncoding RNA

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Financial Support

Financial support provided by the National Basic Research Program of China (973 Program-2013CB944900, 2010CB945300), the National Natural Science Foundation of China (81130058, 81430034), and Research Fund for the Doctoral Program of Higher Education of China (RFDP 20133402110015).

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  1. 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 Xie, Hong-Di Ma & Zhe-Xiong Lian

  2. Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui, 230026,, China

    Zhe-Xiong Lian

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  1. Yu-Qing Xie
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Correspondence to Hong-Di Ma or Zhe-Xiong Lian.

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Xie, YQ., Ma, HD. & Lian, ZX. Epigenetics and Primary Biliary Cirrhosis: a Comprehensive Review and Implications for Autoimmunity. Clinic Rev Allerg Immunol 50, 390–403 (2016). https://doi.org/10.1007/s12016-015-8502-y

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