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of these genes during liver disease. Epigenetic mechanisms dynamically modify gene expression and protein synthesis through histone modification, DNA and RNA methylation, and non-coding RNAs. Cytosines are commonly methylated on their fifth carbon
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not require direct interaction between TR and DNA may also play an important role. In fact, the expression of TH target genes can be modulated via epigenetic mechanisms, including histone modification, DNA methylation, and posttranscriptional silencing
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Objectives
The pathogenesis of Graves’ orbitopathy (GO) remains to be fully elucidated. Here we reviewed the role of genetics and epigenetics.
Design
We conducted a PubMed search with the following key words: Graves’ orbitopathy, thyroid eye disease; or Graves’ ophthalmopathy; or thyroid-associated ophthalmopathy; and: genetic, or epigenetic, or gene expression, or gene mutation, or gene variant, or gene polymorphism, or DNA methylation, or DNA acetylation. Articles in which whole DNA and/or RNA sequencing, proteome and methylome analysis were performed were chosen.
Results
The different prevalence of GO in the two sexes as well as racial differences suggest that genetics play a role in GO pathogenesis. In addition, the long-lasting phenotype of GO and of patient-derived orbital fibroblasts suggest a genetic or epigenetic mechanism. Although no genes have been found to confer a specific risk for GO, differential gene expression has been reported in orbital fibroblasts from GO patients vs control fibroblasts, suggesting that an epigenetic mechanism may be involved. In this regard, a different degree of DNA methylation, which affects gene expression, has been found between GO and control fibroblasts, which was confirmed by whole methylome analysis. Histone acetylation and deacetylation, which also affect gene expression, remain to be investigated.
Conclusions
Although pathogenetic gene variants have not been reported, epigenetic mechanisms elicited by an initial autoimmune insult seem to be needed for differential gene expression to occur and, thus, for GO to develop and persist over time.
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suggested that the increases in neurocognitive and behavioural disabilities, including ASDs and ADHDs, could implicate environmental factors often acting through epigenetic mechanisms (see next section). Moreover, the link to TH-disrupting chemical exposure
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-thyroid drugs such as methimazole or PTU during the foetal and neonatal period of vertebrates results in impairment of hepatic gene expression in adulthood [ 3 , 4 ]. DNA methylation, an epigenetic phenomenon, has been recognized as an interface between
Laboratorio 6, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Instituto Politécnico Nacional, Delegación Tlalpan, Ciudad de México, México
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the fetal physiological systems program the metabolism ( 4 ), and the extrauterine conditions are responsible for modulating the expression of the epigenetic changes ( 5 , 6 ). Some authors speculate that congenital hypothyroidism has an association
University of Lille, Lille, France
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University of Lille, Lille, France
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CRIStAL UMR CNRS 9189, University of Lille, Villeneuve-d’Ascq, France
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University of Lille, Lille, France
Institut National de la Santé et de la Recherche Médicale (INSERM), European Genomic Institute for Diabetes (EGID), CHU Lille, Lille, France
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University of Lille, Lille, France
Institut National de la Santé et de la Recherche Médicale (INSERM), European Genomic Institute for Diabetes (EGID), CHU Lille, Lille, France
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Department of Pathology, Lille University Hospital, Lille, France
University of Lille, CNRS, Inserm, CHU Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity Plasticity and Resistance to Therapies, Lille, France
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instability (MSI) phenotype linked to PMS2 protein expression loss. The expression of MLH1 was more questionable, with nuclear expression by tumor cells judged as weak and partial, a finding observed in patients presenting with MLH1 epigenetic inactivation ( 9
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factors (e.g. viral infection), epigenetic/genetic predispositions, and microbiome of which dysfunction contributes to the loss of immune tolerance, activation of autoreactive lymphocytes, and inflammation, leading to the damage of thyrocytes and clinical
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‘existential’ i.e. the consequence of humans living life to the full. One way in which some environmental and many existential factors may operate is through epigenetic modifications, such as changes in DNA methylation and histone modification, at the tissue
Department of Genetics and Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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regulate 30% of genes encoding proteins. These small regulatory molecules were first identified in 1993. Most of them are located in chromosome fragile sites and are prone to chromosomal removal, movement, and epigenetic changes in various diseases