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J Autoimmun. 2017 Sep;83:43-50. doi: 10.1016/j.jaut.2017.04.003. Epub 2017 Apr 12.

The epigenetic mechanism for discordance of autoimmunity in monozygotic twins.

Author information

1
Department of Laboratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
2
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, United States.
3
Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China. Electronic address: qianlu5860@gmail.com.

Abstract

Monozygotic twins share an identical DNA sequence but are not truly "identical". In fact, when it comes to health and disease, they may often display some level of phenotypic discordance. The cause of this discordance is often unknown. Epigenetic modifications such as DNA methylation, histone modification, and microRNAs-mediated regulation regulate gene expression and are sensitive to external stimuli. These modifications may be seen to bridge the gap between genetics and the environment. Over the years, the importance of epigenetics as a primary mechanism for the role that the environment plays in defining phenotype has been increasingly appreciated. Mechanisms of epigenetics include DNA methylation, histone modifications and microRNAs. Discordance rates in monozygotic twins vary depending on the specific condition, from 11% in SLE to 64% in psoriasis and 77% in PBC. Other autoimmune diseases in which discordance is found among monozygotic twins has also been studied include type 1 diabetes, multiple sclerosis, rheumatoid arthritis, dermatomyositis and systemic sclerosis. In some cases, the differences in various epigenetic modifications is slight, even though the concordance rate is low, suggesting that epigenetics is not the only factor that needs to be considered. Nonetheless, the study of phenotypic discordance in monozygotic twins may shed light on the pathogenesis of autoimmune diseases and contribute to the development of new methodologies for the diagnosis and treatment of these diseases.

KEYWORDS:

Autoimmune diseases; DNA methylation; Epigenetics; Histone modification; MicroRNAs-mediated regulation; Monozygotic twin

PMID:
28412046
DOI:
10.1016/j.jaut.2017.04.003
[Indexed for MEDLINE]

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