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Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age

Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using...

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Autores principales: Crider, Krista S., Quinlivan, Eoin P., Berry, Robert J., Hao, Ling, Li, Zhu, Maneval, David, Yang, Thomas P., Rasmussen, Sonja A., Yang, Quanhe, Zhu, Jiang-Hui, Hu, Dale J., Bailey, Lynn B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233549/
https://www.ncbi.nlm.nih.gov/pubmed/22163281
http://dx.doi.org/10.1371/journal.pone.0028144
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author Crider, Krista S.
Quinlivan, Eoin P.
Berry, Robert J.
Hao, Ling
Li, Zhu
Maneval, David
Yang, Thomas P.
Rasmussen, Sonja A.
Yang, Quanhe
Zhu, Jiang-Hui
Hu, Dale J.
Bailey, Lynn B.
author_facet Crider, Krista S.
Quinlivan, Eoin P.
Berry, Robert J.
Hao, Ling
Li, Zhu
Maneval, David
Yang, Thomas P.
Rasmussen, Sonja A.
Yang, Quanhe
Zhu, Jiang-Hui
Hu, Dale J.
Bailey, Lynn B.
author_sort Crider, Krista S.
collection PubMed
description Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (−14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation.
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spelling pubmed-32335492011-12-12 Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age Crider, Krista S. Quinlivan, Eoin P. Berry, Robert J. Hao, Ling Li, Zhu Maneval, David Yang, Thomas P. Rasmussen, Sonja A. Yang, Quanhe Zhu, Jiang-Hui Hu, Dale J. Bailey, Lynn B. PLoS One Research Article Folate is a source of one-carbons necessary for DNA methylation, a critical epigenetic modification necessary for genomic structure and function. The use of supplemental folic acid is widespread however; the potential influence on DNA methylation is unclear. We measured global DNA methylation using DNA extracted from samples from a population-based, double-blind randomized trial of folic acid supplementation (100, 400, 4000 µg per day) taken for 6 months; including a 3 month post-supplementation sample. We observed no changes in global DNA methylation in response to up to 4,000 µg/day for 6 months supplementation in DNA extracted from uncoagulated blood (approximates circulating blood). However, when DNA methylation was determined in coagulated samples from the same individuals at the same time, significant time, dose, and MTHFR genotype-dependent changes were observed. The baseline level of DNA methylation was the same for uncoagulated and coagulated samples; marked differences between sample types were observed only after intervention. In DNA from coagulated blood, DNA methylation decreased (−14%; P<0.001) after 1 month of supplementation and 3 months after supplement withdrawal, methylation decreased an additional 23% (P<0.001) with significant variation among individuals (max+17%; min-94%). Decreases in methylation of ≥25% (vs. <25%) after discontinuation of supplementation were strongly associated with genotype: MTHFR CC vs. TT (adjusted odds ratio [aOR] 12.9, 95%CI 6.4, 26.0). The unexpected difference in DNA methylation between DNA extracted from coagulated and uncoagulated samples in response to folic acid supplementation is an important finding for evaluating use of folic acid and investigating the potential effects of folic acid supplementation on coagulation. Public Library of Science 2011-12-07 /pmc/articles/PMC3233549/ /pubmed/22163281 http://dx.doi.org/10.1371/journal.pone.0028144 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Crider, Krista S.
Quinlivan, Eoin P.
Berry, Robert J.
Hao, Ling
Li, Zhu
Maneval, David
Yang, Thomas P.
Rasmussen, Sonja A.
Yang, Quanhe
Zhu, Jiang-Hui
Hu, Dale J.
Bailey, Lynn B.
Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age
title Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age
title_full Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age
title_fullStr Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age
title_full_unstemmed Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age
title_short Genomic DNA Methylation Changes in Response to Folic Acid Supplementation in a Population-Based Intervention Study among Women of Reproductive Age
title_sort genomic dna methylation changes in response to folic acid supplementation in a population-based intervention study among women of reproductive age
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3233549/
https://www.ncbi.nlm.nih.gov/pubmed/22163281
http://dx.doi.org/10.1371/journal.pone.0028144
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