Public Defence - September 29: Nicolas Fragoso Bargas

M.Sc. Nicolas Fragoso Bargas at Institute of Clinical Medicine will be defending the thesis “DNA Methylation and cardiometabolic health: associations with insuline resistance, folate, and physical activity in pregnancy” for the degree of PhD (Philosophiae Doctor).

Time and place: Sep. 29, 2023 1:15 PM, Auditoriet i Forskningsbygget (K-bygget), Radiumhospitalet

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 Asians 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 generically 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.

Principal Supervisor
Project Leader Christine Sommer, Oslo University Hospital

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