The whole blood DNA methylation patterns of extrinsic apoptotic signalling pathway-related genes in autoimmune thyroiditis among areas with different iodine levels

Qu, Mengying; Wan, Siyuan; Wu, Hui; Ren, Bingxuan; Chen, Yao; Liu, Lixiang; Shen, Hongmei

doi:10.1017/s0007114522000721

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…One study in the elderly showed that iodine could not modulate the global DNA methylation profile of leukocytes (43) , and another study in animals showed that IE did not change the global methylation levels in lymphocytes (44) . Our previous studies have shown that different iodine levels could affect the methylation patterns of DAPK1 and ITGA6 (45,46) . This study further confirms that iodine status could affect the methylation levels of intrinsic apoptosis genes.…”

Section: Discussionmentioning

confidence: 99%

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene–environment interactions in patients with autoimmune thyroiditis

Zhou

Jin

et al. 2023

Br J Nutr

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Iodine, is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2, and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites, and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation, and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1×ING4_1×BRSK2_1×iodine level) was found to be the best model of the gene-environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4, and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.

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Section: Discussionmentioning

confidence: 99%

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene–environment interactions in patients with autoimmune thyroiditis

Zhou

Jin

et al. 2023

Br J Nutr

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“…In terms of iodine presence in 5-ISA-fortified lettuce, there is little known about potential effects of iodine on DNA methylation in human cells although iodine affects thyroid function and play a role in thyroid cancer and other thyroid disease [ 23 ]. Nevertheless, iodine excess has been shown to affect DNA methylation of selected genes in blood of patients with autoimmune thyroiditis [ 24 , 25 ]. Hence, potential epigenetic effects of iodine cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

“…It is believed that altered patterns of DNA methylation play a role in the progression of cancer and pathogenesis of other disease [ 16 ]. Interestingly, polyphenols from lettuce, iodine, and salicylic acid were all reported to exert certain epigenetic effects [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Effects of Iodine-Biofortified Lettuce in Human Gastrointestinal Cancer Cells

et al. 2022

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Considering the growing number of cancer cases around the world, natural products from the diet that exhibit potential antitumor properties are of interest. Our previous research demonstrated that fortification with iodine compounds is an effective way to improve the antioxidant potential of lettuce. The purpose of the present study was to evaluate the effect of iodine-biofortified lettuce on antitumor properties in human gastrointestinal cancer cell lines, gastric AGS and colon HT-29. Our results showed that extracts from iodine-biofortified lettuce reduce the viability and proliferation of gastric and colon cancer cells. The extracts mediated cell cycle arrest which was accompanied by inactivation of anti-apoptotic Bcl-2 and activation of caspases, as assessed by flow cytometry. However, extracts from lettuce fortified with organic forms of iodine acted more effectively than extracts from control and KIO3-enriched plants. Using quantitative PCR, we detected the increase in pro-apoptotic genes BAD, BAX and BID in AGS cells whereas up-regulation of cell cycle progression inhibitor CDKN2A and downregulation of pro-proliferative MDM2 in HT-29 cells. Interestingly, lettuce extracts led to down-regulation of pro-survival AKT1 and protooncogenic MDM2, which was consistent for extracts of lettuce fortified with organic form of iodine, 5-ISA, in both cell lines. MDM2 downregulation in HT-29 colon cancer cells was associated with RB1 upregulation upon 5-ISA-fortified lettuce extracts, which provides a link to the epigenetic regulation of tumor suppressor genes by RB/MDM2 pathway. Indeed, SEMA3A tumor suppressor gene was hypomethylated and upregulated in HT-29 cells treated with 5-ISA-fortified lettuce. Control lettuce exerted similar effects on RB/MDM2 pathway and SEMA3A epigenetic activation in HT-29 cells. Our findings suggest that lettuce as well as lettuce fortified with organic form of iodine, 5-ISA, may exert epigenetic anti-cancer effects that can be cancer type-specific.

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DNA Methylation in Autoimmune Thyroid Disease

Lafontaine

Wilson

Walsh

2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Graves’ disease and Hashimoto’s disease form part of the spectrum of autoimmune thyroid disease (AITD), to which genetic and environmental factors are recognised contributors. Epigenetics provides a potential link between environmental influences, gene expression and thyroid autoimmunity. DNA methylation (DNAm) is the best studied epigenetic process, and global hypomethylation of leucocyte DNA is reported in several autoimmune disorders. This review summarises current understanding of DNAm in AITD. Targeted DNAm studies of blood samples from AITD patients have reported differential DNAm in the promoter regions of several genes implicated in AITD, including TNF, IFNG, IL2RA, IL6, ICAM1 and PTPN22. In many cases, however, the findings await replication and are unsupported by functional studies to support causal roles in AITD pathogenesis. Furthermore, thyroid hormones affect DNAm, and in many studies confounding by reverse causation has not been considered. Recent studies have shown that DNAm patterns in candidate genes including ITGA6, PRKAA2 and DAPK1 differ between AITD patients from regions with different iodine status, providing a potential mechanism for associations between iodine and AITD. Research focus in the field is moving from candidate gene studies to an epigenome-wide approach. Genome-wide methylation studies of AITD patients have demonstrated multiple differentially methylated positions, including some in immunoregulatory genes such as NOTCH1, HLA-DRB1, TNF and ICAM1. Large, epigenome-wide studies are required to elucidate the pathophysiological role of DNAm in AITD, with the potential to provide novel diagnostic and prognostic biomarkers as well as therapeutic targets.

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The whole blood DNA methylation patterns of extrinsic apoptotic signalling pathway-related genes in autoimmune thyroiditis among areas with different iodine levels

Cited by 3 publications

References 38 publications

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene–environment interactions in patients with autoimmune thyroiditis

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene–environment interactions in patients with autoimmune thyroiditis

Molecular Effects of Iodine-Biofortified Lettuce in Human Gastrointestinal Cancer Cells

DNA Methylation in Autoimmune Thyroid Disease

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