Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk

Claire R. Quilter*, Wendy N. Cooper, Kerry M. Cliffe, Benjamin M. Skinner, Philippa M. Prentice, Latasha Nelson, Julien Bauer, Ken K. Ong, Miguel Constância, William L. Lowe, Nabeel A. Affara, David B. Dunger

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Size at birth, postnatal weight gain, and adult risk for type 2 diabetes may reflect environmental exposures during developmental plasticity and may be mediated by epigenetics. Both low birth weight (BW), as a marker of fetal growth restraint, and high birth weight (BW), especially after gestational diabetes mellitus (GDM), have been linked to increased risk of adult type 2 diabetes. We assessed DNA methylation patterns using a bead chip in cord blood samples from infants of mothers with GDM (group 1) and infants with prenatal growth restraint indicated by rapid postnatal catch-up growth (group 2), compared with infants with normal postnatal growth (group 3). Seventy-five CpG loci were differentially methylated in groups 1 and 2 compared with the controls (group 3), representing 72 genes, many relevant to growth and diabetes. In replication studies using similar methodology, many of these differentially methylated regions were associated with levels of maternal glucose exposure below that defined by GDM [the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study] or were identified as changes observed after randomized periconceptional nutritional supplementation in a Gambian cohort characterized by maternal deprivation. These studies provide support for the concept that similar epigenetic modifications may underpin different prenatal exposures and potentially increase long-term risk for diseases such as type 2 diabetes.-Quilter, C. R., Cooper, W. N., Cliffe, K. M., Skinner, B. M., Prentice, P. M., Nelson, L., Bauer, J., Ong, K. K., Constância, M., Lowe, W. L., Affara, N. A., Dunger, D. B. Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk.

Original languageEnglish (US)
Pages (from-to)4868-4879
Number of pages12
JournalFASEB Journal
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2014

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Keywords

  • Epigenetics
  • Fetal programming
  • Maternal environment

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Quilter, C. R., Cooper, W. N., Cliffe, K. M., Skinner, B. M., Prentice, P. M., Nelson, L., Bauer, J., Ong, K. K., Constância, M., Lowe, W. L., Affara, N. A., & Dunger, D. B. (2014). Impact on offspring methylation patterns of maternal gestational diabetes mellitus and intrauterine growth restraint suggest common genes and pathways linked to subsequent type 2 diabetes risk. FASEB Journal, 28(11), 4868-4879. https://doi.org/10.1096/fj.14-255240