Folate and DNA Methylation

Ly, Anna; Hoyt, Lesley; Crowell, Julie; Kim, Young–In

doi:10.1089/ars.2012.4554

Cited by 90 publications

(64 citation statements)

References 173 publications

(215 reference statements)

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“…El grupo de adultos mayores en ENS 2009-10 (1.043 individuos) fue especialmente sobrerrepresentado en el muestreo, con doble probabilidad de selección en el hogar a través de la tabla de Kish con el objetivo de obtener resultados de precisión estadística similar a los otros grupos de población. De éstos, 827 disponían de valores para folato sérico (FS) y 817 para vitamina B 12 . Los valores extremos (> 62,5 µg/L para folato sérico y > 1.022 pmol/ml para vitamina B 12 ) fueron removidos para la descripción de los promedios y medianas nacionales (se excluyeron los valores 3 veces por sobre o bajo el rango intercuartil).…”

Section: Materials Y Métodounclassified

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Nivel sérico de folato y vitamina B12 en adultos mayores chilenos: Resultados de la Encuesta Nacional de Salud ENS 2009-2010

et al. 2013

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Section: Materials Y Métodounclassified

“…Sin embargo, otros estudios sugieren que niveles elevados podrían determinar efectos adversos en salud también en relación a cáncer [9][10][11][12][13] . En adultos mayores se ha descrito, además, una disminución de la función cognitiva cuando éstos presentan bajos niveles de folato sérico o cuando la elevación está asociada con un déficit de vitamina B 12 14 .…”

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Nivel sérico de folato y vitamina B12 en adultos mayores chilenos: Resultados de la Encuesta Nacional de Salud ENS 2009-2010

et al. 2013

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“…Folate, in the form of 5-methyltetrahydrofolate, is involved in remethylation of homocysteine to methionine, which is a precursor of S-adenosylmethionine (SAM), the primary methyl group donor for most biological methylation reactions including DNA methylation (Kim 2004(Kim , 2005Ly et al 2012). Folate deficiency and excess have been shown to affect DNA methylation in a gene, site, and cell-specific manner (Ly et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Folate deficiency and excess have been shown to affect DNA methylation in a gene, site, and cell-specific manner (Ly et al 2012). DNA methylation is an important epigenetic determinant in gene expression (an inverse relation except for few exceptions), in the maintenance of DNA integrity and stability, in chromatin modifications, and in the development of mutations (Kulis and Esteller 2010).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, GGH modulation may affect DNA methylation by changes in total intracellular folate concentrations and by alterations in contents of polyglutamylated folate cofactors with consequent functional ramifications. Aberrant or dysregulation of DNA methylation is mechanistically related to the development of several human diseases including cancer, and hence, GGH overexpression/inhibition may have significant implications in human health and disease via its effects on DNA methylation (Ly et al 2012). We have recently generated a novel in vitro model of GGH modulation in HCT116 colon and MDA-MB-435 breast cancer cells with predictable functional consequences (Kim et al 2013).…”

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confidence: 99%

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γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells

et al. 2014

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c-Glutamyl hydrolase (GGH) plays an important role in folate homeostasis by catalyzing hydrolysis of polyglutamylated folate into monoglutamates. Polyglutamylated folates are better substrates for several enzymes involved in the generation of S-adenosylmethionine, the primary methyl group donor, and hence, GGH modulation may affect DNA methylation. DNA methylation is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, and in chromatin modifications, and aberrant or dysregulation of DNA methylation has been mechanistically linked to the development of human diseases including cancer. Using a recently developed in vitro model of GGH modulation in HCT116 colon and MDA-MB-435 breast cancer cells, we investigated whether GGH modulation would affect global and gene-specific DNA methylation and whether these alterations were associated with significant gene expression changes. In both cell lines, GGH overexpression decreased global DNA methylation and DNA methyltransferase (DNMT) activity, while GGH inhibition increased global DNA methylation and DNMT activity. Epigenomic and gene expression analyses revealed that GGH modulation influenced CpG promoter DNA methylation and gene expression involved in important biological pathways including cell cycle, cellular development, and cellular growth and proliferation. Some of the observed altered gene expression appeared to be regulated by changes in CpG promoter DNA methylation. Our data suggest that the GGH modulation-induced changes in total intracellular folate concentrations and content of long-chain Electronic supplementary material The online version of this article

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Folate in Human Health and Disease

Warzyszynska

Kim

2014

Encyclopedia of Life Sciences

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Folate, a water‐soluble B vitamin, and its synthetic form folic acid (FA) used in fortification and supplements, are critical to human health due to their role in one‐carbon transfer reactions required for biological methylation and nucleotide biosynthesis. As such, folate deficiency has been linked to a variety of adverse health outcomes such as megaloblastic anaemia, neural tube defects, coronary heart disease and cancer among others. Corollary to this, FA supplementation has garnered a considerable amount of interest as an ideal functional food component for disease prevention. Although the benefits of FA supplementation in treatment of megaloblastic anaemia and in prevention of neural tube defects are well established, the effects of FA supplementation on other disease outcomes remain largely equivocal. In addition, an emerging body of evidence has raised concern regarding potentially serious adverse health effects of excessive FA intake, which warrant further studies. Key Concepts: Folate, a water‐soluble B vitamin, and its synthetic form folic acid used in fortification and supplements, are critical to one‐carbon transfer reactions required for DNA synthesis and biological methylation reactions. Dietary folate intake is the main source of folate for humans; inadequate dietary intake, impaired absorption or metabolism of folate, and increased folate demand and utilisation may result in deficiency. Folate deficiency has been associated with various adverse health effects including megaloblastic anaemia, neural tube defects and other congenital disorders, adverse pregnancy outcomes, neuropsychiatric disorders and cognitive decline, coronary heart disease, stroke and development of some cancers. Folic acid supplementation is effective in treatment of folate‐deficiency associated megaloblastic anaemia and in prevention of neural tube defects. The primary objective of periconceptional folic acid supplementation and mandatory folic acid fortification of the food supply, typically wheat, implemented in North American in 1998, is to prevent neural tube defects. It appears that folic acid fortification has led to up to 50% reduction in the rates of neural tube defects in North America. Folate requirements are increased throughout pregnancy due to rapid growth of the uterus, placenta and foetus, and during lactation as to maintain an adequate folate supply in breast milk for infants. Folate appears to play a dual modulatory role in colorectal carcinogenesis depending on the dose and the stage of cell transformation at the time of folate exposure. Animal studies conducted in colorectal cancer models have shown that folic acid supplementation prevents the development of cancer in normal tissues but promotes the progression of established (pre)neoplastic lesions. Animal studies have also suggested that supraphysiological supplemental doses of folic acid supplementation may promote, rather than prevent cancer development. However, folic acid intervention trials in humans have produced inconsistent results. Although folate deficiency and raised plasma homocysteine levels have been associated with increased risk of coronary heart disease in observational studies; clinical trials have reported largely null effects of folic acid supplementation on the secondary prevention of coronary heart disease. Folate status may play an important role in regulation of epigenetic determinants of gene expression such as DNA methylation relating to its critical role in the provision of S ‐adenosylmethionine, the primary methyl donor in most biological methylation reactions. Excessive folic acid intake from fortified foods and supplements has been linked to certain adverse health effects including masking of vitamin B 12 deficiency and tumour‐progression.

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Folate and DNA Methylation

Cited by 90 publications

References 173 publications

Nivel sérico de folato y vitamina B12 en adultos mayores chilenos: Resultados de la Encuesta Nacional de Salud ENS 2009-2010

Nivel sérico de folato y vitamina B12 en adultos mayores chilenos: Resultados de la Encuesta Nacional de Salud ENS 2009-2010

γ-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells

Folate in Human Health and Disease

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