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Epigenetic signatures of gestational diabetes mellitus on cord blood methylation

BACKGROUND: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these...

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Autores principales: Haertle, Larissa, El Hajj, Nady, Dittrich, Marcus, Müller, Tobias, Nanda, Indrajit, Lehnen, Harald, Haaf, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368916/
https://www.ncbi.nlm.nih.gov/pubmed/28360945
http://dx.doi.org/10.1186/s13148-017-0329-3
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author Haertle, Larissa
El Hajj, Nady
Dittrich, Marcus
Müller, Tobias
Nanda, Indrajit
Lehnen, Harald
Haaf, Thomas
author_facet Haertle, Larissa
El Hajj, Nady
Dittrich, Marcus
Müller, Tobias
Nanda, Indrajit
Lehnen, Harald
Haaf, Thomas
author_sort Haertle, Larissa
collection PubMed
description BACKGROUND: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. METHODS AND RESULTS: Using Illumina’s 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 associated with genes) displayed significant methylation differences between GDM and control samples. Four candidate genes, ATP5A1, MFAP4, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The effects remained significant after adjustment for the confounding factors maternal BMI, gestational week, and fetal sex in a multivariate regression model. In general, GDM effects on FCB methylation were more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. CONCLUSIONS: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis, prognosis, and treatment of adverse prenatal exposures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0329-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-53689162017-03-30 Epigenetic signatures of gestational diabetes mellitus on cord blood methylation Haertle, Larissa El Hajj, Nady Dittrich, Marcus Müller, Tobias Nanda, Indrajit Lehnen, Harald Haaf, Thomas Clin Epigenetics Research BACKGROUND: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. METHODS AND RESULTS: Using Illumina’s 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 associated with genes) displayed significant methylation differences between GDM and control samples. Four candidate genes, ATP5A1, MFAP4, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The effects remained significant after adjustment for the confounding factors maternal BMI, gestational week, and fetal sex in a multivariate regression model. In general, GDM effects on FCB methylation were more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. CONCLUSIONS: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis, prognosis, and treatment of adverse prenatal exposures. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0329-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-03-27 /pmc/articles/PMC5368916/ /pubmed/28360945 http://dx.doi.org/10.1186/s13148-017-0329-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Haertle, Larissa
El Hajj, Nady
Dittrich, Marcus
Müller, Tobias
Nanda, Indrajit
Lehnen, Harald
Haaf, Thomas
Epigenetic signatures of gestational diabetes mellitus on cord blood methylation
title Epigenetic signatures of gestational diabetes mellitus on cord blood methylation
title_full Epigenetic signatures of gestational diabetes mellitus on cord blood methylation
title_fullStr Epigenetic signatures of gestational diabetes mellitus on cord blood methylation
title_full_unstemmed Epigenetic signatures of gestational diabetes mellitus on cord blood methylation
title_short Epigenetic signatures of gestational diabetes mellitus on cord blood methylation
title_sort epigenetic signatures of gestational diabetes mellitus on cord blood methylation
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5368916/
https://www.ncbi.nlm.nih.gov/pubmed/28360945
http://dx.doi.org/10.1186/s13148-017-0329-3
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