dc.contributor.author
Reichetzeder, C.
dc.contributor.author
Putra, S. E. Dwi
dc.contributor.author
Pfab, T.
dc.contributor.author
Slowinski, T.
dc.contributor.author
Neuber, C.
dc.contributor.author
Kleuser, B.
dc.contributor.author
Hocher, B.
dc.date.accessioned
2018-06-08T04:13:03Z
dc.date.available
2016-09-23T09:01:45.900Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/16821
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-21002
dc.description.abstract
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.
en
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Gestational diabetes
dc.subject
Insulin resistance
dc.subject
Global DNA methylation
dc.subject
Hypermethylation
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
dc.title
Increased global placental DNA methylation levels are associated with
gestational diabetes
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Clinical Epigenetics. - 8 (2016), Artikel Nr. 82
dcterms.bibliographicCitation.doi
10.1186/s13148-016-0247-9
dcterms.bibliographicCitation.url
http://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-016-0247-9
refubium.affiliation
Charité - Universitätsmedizin Berlin
de
refubium.mycore.fudocsId
FUDOCS_document_000000025413
refubium.note.author
Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000007095
dcterms.accessRights.openaire
open access