Fat mass and obesity-associated (FTO) gene epigenetic modifications in gestational diabetes: new insights and possible pathophysiological connections

Aims: Gestational diabetes mellitus (GDM) can lead to short- and long-term complications for the child. Epigenetic alterations could contribute to explaining the metabolic disturbances associated with foetal programming. Although the role of the FTO gene remains unclear, it affects metabolic phenotypes probably mediated by epigenetic mechanisms. The aim of this study was to assess whether placental DNA epigenetic modifications at FTO promoter-associated cysteine–phosphate–guanine (CpG) sites are correlated with GDM. A secondary aim was to evaluate the association between the placental FTO DNA methylation and the maternal metabolic traits in women with and without GDM. Methods: Socio-demographic characteristics, clinical parameters at the third trimester of pregnancy, Mediterranean diet adherence, and physical activity were assessed in 33 GDM women and 27 controls. Clinical information about the newborns was registered at birth. The FTO rs9939609 (T > A) was genotyped. Results: No association between FTO DNA methylation and GDM was found. DNA methylation on the maternal side at the CpG1 was associated with maternal smoking in GDM (p = 0.034), and DNA methylation at the CpG3 was correlated with smoking or former smoking in controls (p = 0.023). A higher level of TGs was correlated with higher foetal placental DNA methylation at the CpG2 (p = 0.036) in GDM. An inverse association between HDL-C and maternal placental DNA methylation at the CpG3 in controls (p = 0.045) was found. An association between FTO rs9939609 and neonatal birthweight (p = 0.033) was detected. Conclusions: In the awareness that the obesity pathophysiology is complex, the study adds a piece to this intricate mosaic. © 2021, The Author(s).