Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role

Crider, Krista S.; Yang, Thomas P.; Berry, R. J.; Bailey, Lynn B.

doi:10.3945/an.111.000992

Cited by 788 publications

(621 citation statements)

References 202 publications

(240 reference statements)

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“…We found low B 12 levels to be associated with aberrant allele-specific expression of IGF2, especially among infants with the MTHFR TT/TT genotype. MTHFR converts 5,10-methylene tetrahydrofolate to 5-methyl tetrahydrofolate, which is the methyl donor in homocysteine remethylation to methionine (43,51). The reduced enzymatic activity of MTHFR 677TT genotype may therefore represent a possible explanation of the increased deviation of IGF2 allele-specific expression in the cord blood of TT/TT infants.…”

Section: Discussionmentioning

confidence: 99%

Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1‐carbon metabolism

2017

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Folic acid is an essential component of 1-carbon metabolism, which generates methyl groups for DNA methylation. Disruption of genomic imprinting leads to biallelic expression which may affect disease susceptibility possibly reflected in high levels of S-adenosyl-homocysteine (SAH) and low levels of S-adenosyl-methionine (SAM). We investigated the association between folic acid supplementation during pregnancy and loss of imprinting (LOI) of IGF2 and H19 genes in placentas and cord blood of 90 mother-child dyads in association with the methylenetetrahydrofolate reductase (MTHFR) genotype. Pyrosequencing was used to evaluate deviation from monoallelic expression among 47 placentas heterozygous for H19 and 37 placentas and cord blood tissues heterozygous for IGF2 and H19 methylation levels of 48 placentas. We detected relaxation of imprinting (ROI) and LOI of H19 in placentas not associated with differences in methylation levels of the H19ICR. Placentas retained monoallelic allele-specific gene expression of IGF2, but 32.4% of cord blood samples displayed LOI of IGF2 and 10.8% showed ROI. High SAH levels were significantly associated with low H19 methylation. An interesting positive association between SAM/SAH ratio and high H19 methylation levels was detected among infants with low B 12 levels. Our data suggest profound differences in regulation of imprinting in placenta and cord blood; a lack of correlation of the methylome, transcriptome, and proteome; and a complex regulatory feedback network between free methyl groups and genomic imprinting at birth.-Tserga, A., Binder, A. M., Michels, K. B. Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism. FASEB J. 31, 5149-5158 (2017). www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1‐carbon metabolism

2017

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“…In addition, folic acid is an essential cofactor for the biosynthesis of S-adenosylmethionine (SAM), which is the principal methyl donor in DNA methylation (27). Bone marrow micronucleus assay has been widely used as a screening procedure to evaluate the structural integrity of chromosome and detect potential chromosome damaging agents (28).…”

Section: Discussionmentioning

confidence: 99%

Folic Acid Supplementation Reduces the Mutagenicity and Genotoxicity Caused by Benzo(a)pyrene

Zhang

Zhan

et al. 2016

J Nutr Sci Vitaminol

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Summary Folate is a vital vitamin for the human being and its defi ciency can lead to a variety of clinical abnormalities ranging from neural tube defects to cancers. Benzo(a)pyrene (BaP), a strong mutagen and carcinogen, is considered one of the common contaminants in food. The aim of this study was to investigate the positive effect of folate on cancer prevention at a fundamental level. In the present study, we investigated the impact of folic acid on BaP-induced mutagenicity and genotoxicity by means of in vitro and in vivo experiments. The reformed Ames test was applied to study the antimutagenicity of folic acid against BaP. The protective effect of folic acid on cytotoxicity caused by BaP in human liver cell line L02 was evaluated by MTT assay. In addition, the effect of folic acid on the BaP-induced genotoxicity in vivo was assessed by mouse bone marrow micronucleus assay. The results indicated that folic acid signifi cantly inhibited the reverse mutation of Salmonella typhimurium strains TA98 and TA100, and protected the viability of human liver cells against BaP (pϽ0.01). The micronucleus test showed that all doses of folic acid had a remarkable protective effect for the female mice (pϽ0.01). In conclusion, folic acid was found to reduce the mutagenicity and genotoxicity induced by BaP.

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“…Folates are essential for DNA synthesis, RNA synthesis, methylation reactions, and protein synthesis [6]. The metabolism of folates play a key role in the maintenance of genome integrity due to its role in DNA synthesis, repair, and methylation [7].…”

Section: Introductionmentioning

confidence: 99%

Lack of association between genetic polymorphisms in three folate-related enzyme genes and male infertility in the Chinese population

et al. 2015

J Assist Reprod Genet

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Purpose This study explored the possible association of four single nucleotide polymorphisms (SNPs) of the three folaterelated enzyme genes: MTHFR C677T and A1298C, MTR A2756G and MTRR A66G, with male infertility in the Chinese population. Methods The polymorphic distributions of the four SNPs (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) were investigated by the method of SNaPshot in a Chinese cohort including 296 idiopathic infertile males with azoospermia or oligozoospermia and 204 fertile males. Results We found no evidence for an association between any of these variants (MTHFR C677T and A1298C, MTR A2756G and MTRR A66G) and male infertility. Conclusions There is no evidence for an association between male infertility and polymorphism of the three folate-related enzyme genes in the Chinese population.

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Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role

Cited by 788 publications

References 202 publications

Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1‐carbon metabolism

Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1‐carbon metabolism

Folic Acid Supplementation Reduces the Mutagenicity and Genotoxicity Caused by Benzo(a)pyrene

Lack of association between genetic polymorphisms in three folate-related enzyme genes and male infertility in the Chinese population

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