DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: Results of a pilot randomized controlled trial

Wendy N. Cooper, Batbayar Khulan, Stephen Owens, Cathy E. Elks, Veronica Seidel, Andrew M. Prentice, Gusztav Belteki, Ken K. Ong, Nabeel A. Affara, Miguel Constância, David B. Dunger

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Intrauterine exposures mediated by maternal diet may affect risk of cardiovascular disease, obesity, and type 2 diabetes. Recent evidence, primarily from animal studies and observational data in humans, suggests that the epigenome can be altered by maternal diet during the periconceptional period and that these programming events may underlie later disease risk. A randomized controlled trial of periconceptional micronutrient supplementation in The Gambia, where seasonal nutritional variations affect fetal growth and postnatal outcomes, provided a unique opportunity to test this hypothesis. Specifically, we targeted imprinted genes, which play important roles in allocation of maternal resources while being epigenetically regulated. DNA methylation at 12 differentially methylated regions (DMRs) was analyzed in cord blood samples from 58 offspring of women participating in a doubleblind randomized-controlled trial of pre- and periconceptional micronutrient supplementation (including folate, zinc, and vitamins A, B, C, and D). We observed sex-specific effects of micronutrient supplementation, reducing methylation levels at two of the DMRs analyzed, IGF2R in girls and GTL2-2 in boys. This pilot study is the first to analyze DNA methylation in the context of a randomized controlled trial, and it provides suggestive evidence that periconceptional maternal nutrition alters offspring methylation at imprinted loci.

Original languageEnglish (US)
Pages (from-to)1782-1790
Number of pages9
JournalFASEB Journal
Volume26
Issue number5
DOIs
StatePublished - May 1 2012
Externally publishedYes

Keywords

  • Epigenetics
  • Fetal programming
  • Maternal nutrition

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Cooper, W. N., Khulan, B., Owens, S., Elks, C. E., Seidel, V., Prentice, A. M., Belteki, G., Ong, K. K., Affara, N. A., Constância, M., & Dunger, D. B. (2012). DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: Results of a pilot randomized controlled trial. FASEB Journal, 26(5), 1782-1790. https://doi.org/10.1096/fj.11-192708