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Increased global placental DNA methylation levels are associated with gestational diabetes

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus r...

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Autores principales: Reichetzeder, C., Dwi Putra, S. E., Pfab, T., Slowinski, T., Neuber, C., Kleuser, B., Hocher, B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960714/
https://www.ncbi.nlm.nih.gov/pubmed/27462376
http://dx.doi.org/10.1186/s13148-016-0247-9
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author Reichetzeder, C.
Dwi Putra, S. E.
Pfab, T.
Slowinski, T.
Neuber, C.
Kleuser, B.
Hocher, B.
author_facet Reichetzeder, C.
Dwi Putra, S. E.
Pfab, T.
Slowinski, T.
Neuber, C.
Kleuser, B.
Hocher, B.
author_sort Reichetzeder, C.
collection PubMed
description BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus regarding placental epigenetic changes in GDM was set on gene-specific DNA methylation analyses. Studies that robustly investigated placental global DNA methylation are lacking. However, several studies showed that tissue-specific alterations in global DNA methylation are independently associated with type 2 diabetes. Thus, the aim of this study was to characterize global placental DNA methylation by robustly measuring placental DNA 5-methylcytosine (5mC) content and to examine whether differences in placental global DNA methylation are associated with GDM. METHODS: Global DNA methylation was quantified by the current gold standard method, LC-MS/MS. In total, 1030 placental samples were analyzed in this single-center birth cohort study. RESULTS: Mothers with GDM displayed a significantly increased global placental DNA methylation (3.22 ± 0.63 vs. 3.00 ± 0.46 %; p = 0.013; ±SD). Bivariate logistic regression showed a highly significant positive correlation between global placental DNA methylation and the presence of GDM (p = 0.0009). Quintile stratification according to placental DNA 5mC levels revealed that the frequency of GDM was evenly distributed in quintiles 1–4 (2.9–5.3 %), whereas the frequency in the fifth quintile was significantly higher (10.7 %; p = 0.003). Bivariate logistic models adjusted for maternal age, BMI, ethnicity, recurrent miscarriages, and familiar diabetes predisposition clearly demonstrated an independent association between global placental DNA hypermethylation and GDM. Furthermore, an ANCOVA model considering known predictors of DNA methylation substantiated an independent association between GDM and placental DNA methylation. CONCLUSIONS: This is the first study that employed a robust quantitative assessment of placental global DNA methylation in over a thousand placental samples. The study provides large scale evidence that placental global DNA hypermethylation is associated with GDM, independent of established risk factors.
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spelling pubmed-49607142016-07-27 Increased global placental DNA methylation levels are associated with gestational diabetes Reichetzeder, C. Dwi Putra, S. E. Pfab, T. Slowinski, T. Neuber, C. Kleuser, B. Hocher, B. Clin Epigenetics Research BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus regarding placental epigenetic changes in GDM was set on gene-specific DNA methylation analyses. Studies that robustly investigated placental global DNA methylation are lacking. However, several studies showed that tissue-specific alterations in global DNA methylation are independently associated with type 2 diabetes. Thus, the aim of this study was to characterize global placental DNA methylation by robustly measuring placental DNA 5-methylcytosine (5mC) content and to examine whether differences in placental global DNA methylation are associated with GDM. METHODS: Global DNA methylation was quantified by the current gold standard method, LC-MS/MS. In total, 1030 placental samples were analyzed in this single-center birth cohort study. RESULTS: Mothers with GDM displayed a significantly increased global placental DNA methylation (3.22 ± 0.63 vs. 3.00 ± 0.46 %; p = 0.013; ±SD). Bivariate logistic regression showed a highly significant positive correlation between global placental DNA methylation and the presence of GDM (p = 0.0009). Quintile stratification according to placental DNA 5mC levels revealed that the frequency of GDM was evenly distributed in quintiles 1–4 (2.9–5.3 %), whereas the frequency in the fifth quintile was significantly higher (10.7 %; p = 0.003). Bivariate logistic models adjusted for maternal age, BMI, ethnicity, recurrent miscarriages, and familiar diabetes predisposition clearly demonstrated an independent association between global placental DNA hypermethylation and GDM. Furthermore, an ANCOVA model considering known predictors of DNA methylation substantiated an independent association between GDM and placental DNA methylation. CONCLUSIONS: This is the first study that employed a robust quantitative assessment of placental global DNA methylation in over a thousand placental samples. The study provides large scale evidence that placental global DNA hypermethylation is associated with GDM, independent of established risk factors. BioMed Central 2016-07-26 /pmc/articles/PMC4960714/ /pubmed/27462376 http://dx.doi.org/10.1186/s13148-016-0247-9 Text en © The Author(s). 2016 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
Reichetzeder, C.
Dwi Putra, S. E.
Pfab, T.
Slowinski, T.
Neuber, C.
Kleuser, B.
Hocher, B.
Increased global placental DNA methylation levels are associated with gestational diabetes
title Increased global placental DNA methylation levels are associated with gestational diabetes
title_full Increased global placental DNA methylation levels are associated with gestational diabetes
title_fullStr Increased global placental DNA methylation levels are associated with gestational diabetes
title_full_unstemmed Increased global placental DNA methylation levels are associated with gestational diabetes
title_short Increased global placental DNA methylation levels are associated with gestational diabetes
title_sort increased global placental dna methylation levels are associated with gestational diabetes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4960714/
https://www.ncbi.nlm.nih.gov/pubmed/27462376
http://dx.doi.org/10.1186/s13148-016-0247-9
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