.jpg)
Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Matthew Suderman, University of Bristol, UK
- Second opponent: Researcher Therese Haugdal Nøst, NTNU and UiT, Norway
- Third member and chair of the evaluation committee: Professor Benedicte Alexandra Lie, University of Oslo
Chair of the Defence
Associate Professor Per Medbøe Thorsby, University of Oslo
Principal Supervisor
Project Leader Christine Sommer, Oslo University Hospital
Summary
DNA methylation is a plastic mark that can be affected by genetics and several exposures from an individual’s lifestyle and the environment. In this thesis I have explored the association between DNA methylation in maternal peripheral blood leukocytes with insulin resistance, serum folate and physical activity, in a cohort of pregnant women of European and South Asian ethnicity.
In the EPIPREG (Epigenetics in pregnancy) sample (n=480), DNA methylation was quantified in peripheral blood leukocytes in gestational week 28. We identified that methylation at six CpG sites were associated with insulin resistance, whereof five were replicated in external cohorts. Three of the replicated CpG sites were located in the TXNIP gene, which has been previously related with type 2 diabetes and metabolic syndrome. Serum folate have been associated with lower risk for some cardiometabolic outcomes and is vital for DNA methylation maintenance. Thus, DNA methylation has been proposed to be an intermediate mechanism between folate and its associated cardiometabolic phenotypes. Serum folate was associated with methylation at three CpG sites previously not reported in the literature. However, we did not find strong evidence that the CpG sites associated with serum folate were associated with cardiometabolic related traits as well. Lastly, we identified that methylation at several CpG sites were associated with hours moderate physical activity and two with hours of sedentary behavior. Some of the CpG sites identified across the studies had mQTLs (Methyl quantitative trait loci), indicating that the methylation of these sites could be genetically regulated.
The findings of this thesis could be useful to improve our understanding of the molecular etiology of gestational diabetes, type 2 diabetes and related cardiovascular diseases. Epigenetic signatures may in the future serve as biomarkers for diabetes prevention and point to potential molecular targets for pharmacological interventions.
Additional information
Contact the research support staff.