Gene-gene and gene-sex epistatic interactions of &lt;i&gt;DNMT1&lt;/i&gt;, &lt;i&gt;DNMT3A&lt;/i&gt; and &lt;i&gt;DNMT3B&lt;/i&gt; in autoimmune thyroid disease

Cai, Tiantian; Zhang, Jian; Wang, Xuan; Song, Ronghua; Qin, Qiu; Muhali, Fatuma-Said; Zhou, Jiao-zhen; Xu, Jianhua; Zhang, Jinan

doi:10.1507/endocrj.ej15-0596

Cited by 18 publications

(8 citation statements)

References 40 publications

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“…Arakawa et al reported that several polymorphisms in methylation-regulating genes, such as DNMT1 and methionine synthase reductase ( MTRR ), were correlated with DNA hypomethylation levels and susceptibility to AITD (91). Our previous study also found evidence for a potential role of DNMT3B rs2424913 and DNMT1 rs2228611 in the susceptibility to AITD (92). 5,10-Methylenetetrahydrofolate reductase C677T polymorphism was also associated with GD and Graves’ ophthalmopathy (93, 94).…”

Section: Epigenetics In Aitdsupporting

confidence: 53%

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

et al. 2017

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Autoimmune thyroid diseases (AITD) are a group of both B cell- and T cell-mediated organ-specific autoimmune diseases. Graves’ disease and Hashimoto thyroiditis are the two main clinical presentations of AITD. Both genetic and environmental factors have important roles in the development of AITD. Epigenetics have been considered to exert key roles in integrating those genetic and environmental factors, and epigenetic modifications caused by environmental factors may drive genetically susceptibility individuals to develop AITD. Recent studies on the epigenetics of AITD have provided some novel insights into the pathogenesis of AITD. The aim of this review is to provide an overview of recent advances in the epigenetic mechanisms of AITD, such as DNA methylation, histone modifications, and non-coding RNAs. This review highlights the key roles of epigenetics in the pathogenesis of AITD and potential clinical utility. However, the epigenetic roles in AITD are still not fully elucidated, and more researches are needed to provide further deeper insights into the roles of epigenetics in AITD and to uncover new therapeutic targets. Although there are many studies assessing the epigenetic modifications in AITD patients, the clinical utility of epigenetics in AITD remains poorly defined. More studies are needed to identify the underlying epigenetic modifications that can contribute to accurate diagnosis of AITD, adequate choice of treatment approach, and precise prediction of treatment outcomes.

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Section: Epigenetics In Aitdsupporting

confidence: 53%

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

et al. 2017

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“…On the other hand, 148 differentially methylated sites, including CD14, IL17RE and DRD4, were also associated with GD, particularly with Graves' orbitopathy . All these results are in accordance with previous studies, in which certain single nucleotide polymorphisms in genes encoding DNA methyltransferases DNMT1, DNMT3B, methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), which are all enzymes essential for DNA methylation, were associated with either susceptibility to, severity or protection against AITD . Besides, newly diagnosed GD patients were also found to present global DNA hypomethylation and lower DNMT1 expression in T and B lymphocytes .…”

Section: Discussionsupporting

confidence: 90%

“…46 All these results are in accordance with previous studies, in which certain single nucleotide polymorphisms in genes encoding DNA methyltransferases DNMT1, DNMT3B, methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), which are all enzymes essential for DNA methylation, were associated with either susceptibility to, severity or protection against AITD. [47][48][49][50] Besides, newly diagnosed GD patients were also found to present global DNA hypomethylation and lower DNMT1 expression in T and B lymphocytes. 51 Finally, in disparity with all previous studies that reported changes of DNA methylation in blood cells, one study revealed aberrant DNA methylation in thyroid gland cells of AITD patients, particularly within the ICAM1 gene promoter, along with increased gene expression.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation analysis within the IL2RA gene promoter in youth with autoimmune thyroid disease

Kyrgios

Fragou

Kotanidou

et al. 2020

Eur J Clin Investigation

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Background Alpha‐subunit of the interleukin‐2 receptor (IL2RA) is involved in the regulation of T‐cell function and has been related to autoimmune thyroid disease (AITD). Although the exact mechanisms are not fully understood, promoter methylation might account for differences in gene expression. The aim of this study was to investigate whether there are differences in the percentage of DNA methylation within the IL2RA gene promoter in young patients with AITD. Materials and methods In a cross‐sectional design, the presence of DNA methylation in the IL2RA gene promoter was quantified, by real‐time PCR and melting curve analysis, in modified genomic DNA isolated from blood samples of a total of 149 children and adolescents with AITD, including patients with Hashimoto thyroiditis (ΗΤ) (n = 60), Graves' disease (GD) (n = 9), concurrent diagnosis of HT and type 1 diabetes (T1DM + HT) (n = 25), and healthy controls (n = 55). Results The percentage of DNA methylation in the IL2RA gene promoter was significantly decreased in patients with GD (26.0 ± 4.2%) but not in those with HT (36.3 ± 1.4%) in comparison with controls (41.3 ± 1.5%). Conclusions The observed DNA hypomethylation in the IL2RA gene promoter in patients with GD might be related to its increased expression, thus contributing to the etiopathogenesis of GD in childhood and adolescence.

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“…For what is concerning AITD there is increasing evidence of epigenetic changes in these conditions, but the available studies are still limited (Table 1) to be translated into the clinical settings. Particularly, the two available genome-wide DNA methylation studies in blood AITD cells are limited to GD patients (31, 32), and one of them included only three patients and three matched controls (27) making it difficult to clearly discriminate disease-specific epigenetic changes from others that could result from interindividual variability. Also data concerning histone tail modifications are mainly available from GD patients (32, 36), and lack of similar epigenome-wide data in cells from HT individuals does not allow comparing the two conditions in terms of epigenetic differences or similarities, so that the diagnostic values of the observed epigenetic changes and their potential prognostic utility are not yet clearly defined.…”

Section: Discussionmentioning

confidence: 99%

“…rs1801133 in MTHFR was associated with reduced GD risk in women (25), while rs2228612 in DNMT1 was linked to DNA hypomethylation and with the intractability of GD and rs1801394 in MTRR with the severity of HT (26). A more recent study addressed the contribution of DNMT gene polymorphisms in a large cohort of AITD patients composed by a total of 685 GD patients, 353 HT patients, and 909 healthy controls, revealing that both rs2424913 in DNMT3B and rs2228611 in DNMT1 were associated with AITD susceptibility (27). Interestingly, DNMT gene polymorphisms have been associated with other autoimmune disorders, for example DNMT3B polymorphisms were linked to increased risk of oral lichen planus (28), with the progression of joint destruction in RA (29), and with increased risk of thymoma in patients with myasthenia gravis (30).…”

Section: Dna Methylation In Aitdmentioning

confidence: 99%

Epigenetics and Autoimmune Thyroid Diseases

Coppedè

2017

Front. Endocrinol.

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Increasing evidence suggests that epigenetic modifications, including changes in DNA methylation, covalent modifications of histone tails, and gene silencing mediated by non-coding RNA molecules, play a substantial role in the pathogenesis of autoimmune disorders and might be seen as the result of environmental insults that trigger these conditions. Studies in cells and tissues of patients with autoimmune thyroid diseases (AITD), and particularly in Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), are increasingly revealing altered epigenetic marks and resultant deregulation of gene expression levels, but the available data are still limited to be translated into the clinical settings. Particularly, genome-wide methylation and histone tail modification screenings are limited to a few studies in GD patients, and the diagnostic values of the observed epigenetic changes or their potential prognostic utility are still unclear. Similarly, data concerning microRNA expression in AITD patients are largely descriptive and not yet translated into the clinics. In addition, studies relating certain environmental exposures to specific epigenetic changes in AITD and studies evaluating the crosstalk between different epigenetic mechanisms are largely missing. In summary, despite that there is a clear evidence of epigenetic impairment in AITD, further research is required for a better understanding of the epigenetic networks involved in disease pathogenesis, thereby opening the way for potential diagnostic and prognostic tools, as well as for epigenetic interventions in the patients.

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Gene-gene and gene-sex epistatic interactions of <i>DNMT1</i>, <i>DNMT3A</i> and <i>DNMT3B</i> in autoimmune thyroid disease

Cited by 18 publications

References 40 publications

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

DNA methylation analysis within the IL2RA gene promoter in youth with autoimmune thyroid disease

Epigenetics and Autoimmune Thyroid Diseases

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