Epigenetic differences after prenatal adversity : the Dutch hunger winter

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Epigenetic differences after prenatal adversity : the Dutch hunger winter

Title: Epigenetic differences after prenatal adversity : the Dutch hunger winter
Author: Tobi, Elmar Wouter
Publisher: Molecular Epidemiology, Faculty of Medicine / Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2013-10-29
Keywords: Development
Epigenetics
DOHAD
DNA methylation
Dutch Famine
IGF2
IUGR
SGA
Malnutrition
Hunger winter
Abstract: This thesis is a study on the link between early development and adult health. Studies in animal models indicate that so-called epigenetic marks may be influenced by nutrition during development, changing the expression of genes implicated in disease. Epigenetics may therefore link development and disease. To investigate this hypothesis in humans we studied DNA methylation, a key epigenetic mark, in individuals exposed during early gestation to the Dutch Famine and individuals born growth restricted, which is also alleged to relate to malnutrition. DNA methylation at metabolic and developmental genes was associated with early gestational famine exposure to the Dutch Famine and the patterns of the associations mirrored the epidemiological findings. The associations found with prenatal famine exposure did not relate to prenatal growth restriction, adding evidence that prenatal growth restriction is not linked with m alnutrition in Western cohorts. Further characterization showed that DNA methylation differences associated with prenatal famine exposure are independent of genetic variation, cluster along biological pathways and within regulatory regions and may relate to the phenotypic consequences of prenatal malnutrition. The work described in this thesis gives credence to the hypothesis that epigenetic marks may be the molecular link between development and later disease in humans
Description: Promotor: P.E.Slagboom, Co-promotores: B.T. Heijmans, L.H. Lumey
With summary in Dutch
Faculty: LUMC
Citation: Tobi, E.W., 2013, Doctoral thesis, Leiden University
ISBN: 97890-88917141
Sponsor: The Netherlands Consortium for Healthy Ageing (NCHA)
Handle: http://hdl.handle.net/1887/22065
 

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