Epigenetic signatures of gestational diabetes mellitus on cord blood methylation
Abstract 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 media...
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| Format: | Article |
| Language: | English |
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BMC
2017-03-01
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| Series: | Clinical Epigenetics |
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| Online Access: | http://link.springer.com/article/10.1186/s13148-017-0329-3 |
| _version_ | 1818243262195957760 |
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| author | Larissa Haertle Nady El Hajj Marcus Dittrich Tobias Müller Indrajit Nanda Harald Lehnen Thomas Haaf |
| author_facet | Larissa Haertle Nady El Hajj Marcus Dittrich Tobias Müller Indrajit Nanda Harald Lehnen Thomas Haaf |
| author_sort | Larissa Haertle |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T13:58:20Z |
| format | Article |
| id | doaj.art-170cb92398bd41cfb9fd6258ba765f79 |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-12T13:58:20Z |
| publishDate | 2017-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-170cb92398bd41cfb9fd6258ba765f792022-12-22T00:22:24ZengBMCClinical Epigenetics1868-70751868-70832017-03-019111110.1186/s13148-017-0329-3Epigenetic signatures of gestational diabetes mellitus on cord blood methylationLarissa Haertle0Nady El Hajj1Marcus Dittrich2Tobias Müller3Indrajit Nanda4Harald Lehnen5Thomas Haaf6Institute of Human Genetics, Julius-Maximilians-Universität Würzburg, BiozentrumInstitute of Human Genetics, Julius-Maximilians-Universität Würzburg, BiozentrumInstitute of Human Genetics, Julius-Maximilians-Universität Würzburg, BiozentrumDepartment of Bioinformatics, Julius Maximilians UniversityInstitute of Human Genetics, Julius-Maximilians-Universität Würzburg, BiozentrumDepartment of Gynecology and Obstetrics, Municipal ClinicsInstitute of Human Genetics, Julius-Maximilians-Universität Würzburg, BiozentrumAbstract 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.http://link.springer.com/article/10.1186/s13148-017-0329-3DNA methylationFetal cord bloodFetal programmingGestational diabetes mellitusInsulin treatment |
| spellingShingle | Larissa Haertle Nady El Hajj Marcus Dittrich Tobias Müller Indrajit Nanda Harald Lehnen Thomas Haaf Epigenetic signatures of gestational diabetes mellitus on cord blood methylation Clinical Epigenetics DNA methylation Fetal cord blood Fetal programming Gestational diabetes mellitus Insulin treatment |
| 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 | DNA methylation Fetal cord blood Fetal programming Gestational diabetes mellitus Insulin treatment |
| url | http://link.springer.com/article/10.1186/s13148-017-0329-3 |
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