LRP1B, BRD2 and CACNA1D: new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia

Epigenomics. 2015 Oct;7(7):1111-22. doi: 10.2217/epi.15.72. Epub 2015 Nov 20.

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: DNA methylation; cord blood; epigenetics; gestational diabetes; placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Birth Weight
  • Blood Glucose / metabolism
  • Calcium Channels, L-Type / genetics*
  • Calcium Channels, L-Type / metabolism
  • Cohort Studies
  • DNA Methylation
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / genetics*
  • Diabetes, Gestational / physiopathology
  • Energy Metabolism / genetics
  • Epigenesis, Genetic*
  • Female
  • Fetal Blood / metabolism
  • Fetal Development / genetics
  • Fetus
  • Humans
  • Hyperglycemia / blood
  • Hyperglycemia / genetics*
  • Hyperglycemia / physiopathology
  • Infant, Newborn
  • Male
  • Placenta / metabolism
  • Pregnancy
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Receptors, LDL / genetics*
  • Receptors, LDL / metabolism
  • Transcription Factors

Substances

  • BRD2 protein, human
  • Blood Glucose
  • CACNA1D protein, human
  • Calcium Channels, L-Type
  • LRP1B protein, human
  • Receptors, LDL
  • Transcription Factors
  • Protein Serine-Threonine Kinases