LRP1B, BRD2 and CACNA1D: New Candidate Genes in Fetal Metabolic Programming of Newborns Exposed to Maternal Hyperglycemia

Abstract

Aim: To assess the associations between gestational diabetes mellitus (GDM) and DNA methylation levels at genes related to energy metabolism. Patients & methods: Ten loci were selected from our recent epigenome-wide association study on GDM. DNA methylation levels were quantified by bisulfite pyrosequencing in 80 placenta and cord blood samples (20 exposed to GDM) from an independent birth cohort (Gen3G). Results: We did not replicate association between DNA methylation and GDM. However, in normoglycemic women, glucose levels were associated with DNA methylation changes at LRP1B and BRD2 and at CACNA1D and LRP1B gene loci in placenta and cord blood, respectively. Conclusion: These results suggest that maternal glucose levels, within the normal range, are associated with DNA methylation changes at genes related to energy metabolism and previously associated with GDM. Maternal glycemia might thus be involved in fetal metabolic programming.

Keywords::

• cord blood
• DNA methylation
• epigenetics
• gestational diabetes
• placenta

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi.15.72

Acknowledgements

The authors acknowledge the Blood Sampling Clinic in pregnancy at Centre Hospitalier Universitaire de Sherbrooke (CHUS), which supports research activities integrated to the Blood Sampling in pregnancy Clinic; the CHUS laboratory for performing blood glucose and lipid profile analyses; and the contribution of the clinical research nurses (M Gérard, CHUS; G Proulx, CHUS; S Hayes, CHUS; and M-J Gosselin, CHUS) and research assistants (C Rousseau, CHUS; P Brassard, CHUS; J Ménard, CHUS; MC Battista, CHUS and S Claveau, ECOGENE-21 laboratory) and graduate students (L Guillemette, M Lacroix, J Patenaude) for their dedicated work in this study. The authors also express their gratitude to C Bélanger, Chicoutimi Hospital, for her thoughtful language revision of the manuscript.

Financial & competing interests disclosure

This project was supported by ECOGENE-21 Clinical Research Center, the Canadian Institutes of Health Research (CIHR), the Fonds de Recherche du Québec en Santé (FRQS) and Diabète Québec. L Bouchard is a Junior Research Scholar from the Fonds de la Recherche en Santé du Québec (FRQS). M-F Hivert was an FRSQ Research Scholar and was awarded Clinical Scientist award by the Canadian Diabetes Association (CDA); she is now supported by American Heart Association (AHA) and American Diabetes Association (ADA) awards. L Bouchard and M-F Hivert are members of the FRQS-funded Centre de recherche Clinique Étienne-Le Bel (affiliated with Centre Hospitalier Universitaire de Sherbrooke [CHUS]). A-A Houde is the recipient of doctoral training award from the FRQS and the Faculté de Médecine et des Sciences de la Santé de l’Université de Sherbrooke. S-M Ruchat has received a postdoctoral fellowship from the CDA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This project was supported by ECOGENE-21 Clinical Research Center, the Canadian Institutes of Health Research (CIHR), the Fonds de Recherche du Québec en Santé (FRQS) and Diabète Québec. L Bouchard is a Junior Research Scholar from the Fonds de la Recherche en Santé du Québec (FRQS). M-F Hivert was an FRSQ Research Scholar and was awarded Clinical Scientist award by the Canadian Diabetes Association (CDA); she is now supported by American Heart Association (AHA) and American Diabetes Association (ADA) awards. L Bouchard and M-F Hivert are members of the FRQS-funded Centre de recherche Clinique Étienne-Le Bel (affiliated with Centre Hospitalier Universitaire de Sherbrooke [CHUS]). A-A Houde is the recipient of doctoral training award from the FRQS and the Faculté de Médecine et des Sciences de la Santé de l’Université de Sherbrooke. S-M Ruchat has received a postdoctoral fellowship from the CDA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.