DNA methylation and fluoride exposure in school-age children: Epigenome-wide screening and population-based validation

Wang, Anqi; Ma, Qiang; Gong, Biao; Sun, Long; Afrim, Francis-Kojo; Sun, Renjie; He, Tongkun; Huang, Hui; Zhu, Jingyuan; Zhou, Guoyu; Ba, Yue

doi:10.1016/j.ecoenv.2021.112612

Cited by 9 publications

(4 citation statements)

References 40 publications

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“…Its increase may be also related to the organisms attempt to maintain translation in the presence of F. Recent studies have shown that F-induced hypermethylation in key genes is involved in distinct toxicity effects. 37 - 39 …”

Section: Discussionmentioning

confidence: 99%

Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses

et al. 2023

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Fluoride (F) has been widely used to control dental caries, and studies suggest beneficial effects against diabetes when a low dose of F is added to the drinking water (10 mgF/L). Objectives This study evaluated metabolic changes in pancreatic islets of NOD mice exposed to low doses of F and the main pathways altered by the treatment. Methodology In total, 42 female NOD mice were randomly divided into two groups, considering the concentration of F administered in the drinking water for 14 weeks: 0 or 10 mgF/L. After the experimental period, the pancreas was collected for morphological and immunohistochemical analysis, and the islets for proteomic analysis. Results In the morphological and immunohistochemical analysis, no significant differences were found in the percentage of cells labelled for insulin, glucagon, and acetylated histone H3, although the treated group had higher percentages than the control group. Moreover, no significant differences were found for the mean percentages of pancreatic areas occupied by islets and for the pancreatic inflammatory infiltrate between the control and treated groups. Proteomic analysis showed large increases in histones H3 and, to a lesser extent, in histone acetyltransferases, concomitant with a decrease in enzymes involved in the formation of acetyl-CoA, besides many changes in proteins involved in several metabolic pathways, especially energy metabolism. The conjunction analysis of these data showed an attempt by the organism to maintain protein synthesis in the islets, even with the dramatic changes in energy metabolism. Conclusion Our data suggests epigenetic alterations in the islets of NOD mice exposed to F levels comparable to those found in public supply water consumed by humans.

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Section: Discussionmentioning

confidence: 99%

Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses

et al. 2023

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“…However, one-carbon metabolism nutrients may influence fluorosis by means of their antioxidant properties, as they are well documented antioxidant compounds that reduce the risk of diseases ( 53 , 54 ). Furthermore, DNA methylation plays an important role in fluorosis ( 55 ), one-carbon metabolism nutrients as methyl donors may prevent the change of DNA methylation induced by fluoride. Further studies are warranted to elucidate the competing pathophysiological mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Association between dietary intake of one-carbon metabolism nutrients and hyperglycemia in coal-burning fluorosis areas of Guizhou, China

et al. 2022

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Background and aimsThere are limited studies describing the association between dietary intake of one-carbon metabolism nutrients and hyperglycemia. The present study aimed to investigate the association of habitual dietary intake of one-carbon metabolism nutrients with hyperglycemia in a fluorosis area in China, and explored the interaction between these nutrients and fluorosis related to hyperglycemia.MethodIn a cross-sectional study, we recruited 901 villagers, ages ranging from 18–75, in Guizhou Province. Dietary data and other covariate data were obtained through an interviewer-administered questionnaire. We collected venous blood samples from participants who had fasted for one night to obtain fasting blood glucose levels and we categorized dietary intake of betaine, total choline, methionine, folate, vitamins B6 and B12, and choline subclasses into quartiles (Q1–Q4). The lowest quartile (Q1) served as the reference group. An unconditional logistic regression model was used to evaluate the protective effects of a dietary intake of one-carbon nutrients against hyperglycemia. We calculated Odds Ratios (ORs) with 95% confidence intervals (CIs). A presence or absence of fluorosis subgroup analysis was performed to determine the potential effect of fluorosis on hyperglycemia.ResultAfter adjusting for potential confounding factors, we found that a greater intake of dietary vitamin B6, total choline and methyl-donor index was inversely associated with the occurrence of hyperglycemia (P-trend <0.05). However, there were no significant associations between hyperglycemia and the dietary intake of folate, vitamin B12, methionine, and betaine. As for the choline subgroups, it showed that the dietary intake of free choline, phosphatidylcholine, and glycerol phosphatidylcholine was negatively correlated with the occurrence of hyperglycemia (P < 0.05). In contrast, there was no statistical association between dietary phosphatidylcholine and sphingomyelin and hyperglycemia (all P > 0.05). The results of subgroup analysis showed that dietary intake of folate, vitamin B6, total choline, free choline, glycerol phosphorylcholine, and phosphocholine had a protective effect against the occurrence of hyperglycemia in the non-fluorosis subgroup, although no effects were observed in the fluorosis subgroup. There were significant interactions between these nutrients and fluorosis (P = 0.010–0.048).ConclusionThe study demonstrated that higher dietary intake of vitamin B6, total choline, methyl-donor index, free choline, glycerol phosphorylcholine, and phosphocholine in choline compounds were associated with a lower incidence of hyperglycemia. Moreover, the associations were modified by the presence or absence of fluorosis. Further investigation is needed to test the association in large-scale follow-up studies.

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“…Fluoride intake is widely ubiquitous as it can be ingested daily unintendedly via foods, drinking water, and dental products constituting a continuous long-term exposure. Even though fluoride may be an effective prophylactic against caries, particularly in children ( USDHHS, 2015 ), increased fluoride exposures may also contribute to long-term deleterious effects, such as fluorosis ( Holt et al, 1994 ; Tavener et al, 2006 ; Wong et al, 2010 ), DNA methylation changes ( Wang et al, 2021 ), or neurological effects ( Ding and Yanhui-Gao, 2011 ; Xu et al, 2020 ; Yu et al, 2018 ; Wang et al, 2007 ; Malin and Till, 2015 ; Bashash et al, 2017 ; Choi et al, 2012 ), as shown in previous cross-sectional studies, prospective studies, and clinical trials ( Holt et al, 1994 ; Tavener et al, 2006 ; Wong et al, 2010 ; Wang et al, 2021 ; Ding and YanhuiGao, 2011 ; Xu et al, 2020 ; Yu et al, 2018 ; Wang et al, 2007 ; Malin and Till, 2015 ; Bashash et al, 2017 ; Choi et al, 2012 ). Similar effects have also been observed in experimental studies in animals, and, to a lesser extent, in epidemiological studies in adults, including fluorosis ( Everett, 2011 ), bone fractures ( Li et al, 2001 ), carcinogenicity ( Bucher et al, 1991 ), high blood pressure ( Yousefi et al, 2018 ), liver function ( Lu et al, 2017 ; Wang et al, 2019 ; Shanthakumari et al, 2004 ; Guo et al, 2003 ; Chattopadhyay et al, 2011 ; de Camargo and Merzel, 1980 ; Chen et al, 2013 ), insulin and glucose metabolism impairment ( Itai et al, 2021 ; Trivedi et al, 1993 ), or endocrine sex-steroid and thyroid hormone disruption ( Basha et al, 2011 ; Shoback and McGhee, 1988 ; Chen et al, 1988 ; Puranik et al, 2015 ; Skórka-Majewicz et al, 2020 ; Thippeswamy et al, 2021 ; Kumar et al, 2018 ; Kheradpisheh et al, 2018 ; Ortiz-Pérez et al, 2003 ; Ma et al, 2017 ; Zhou et al,...…”

Section: Introductionmentioning

confidence: 99%

Longitudinal associations between early-life fluoride exposures and cardiometabolic outcomes in school-aged children

India Aldana,

Colicino,

Cantoral Preciado

et al. 2024

Environment International

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DNA methylation and fluoride exposure in school-age children: Epigenome-wide screening and population-based validation

Cited by 9 publications

References 40 publications

Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses

Metabolic effect of low fluoride levels in the islets of NOD mice: integrative morphological, immunohistochemical, and proteomic analyses

Association between dietary intake of one-carbon metabolism nutrients and hyperglycemia in coal-burning fluorosis areas of Guizhou, China

Longitudinal associations between early-life fluoride exposures and cardiometabolic outcomes in school-aged children

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