Folate in pregnancy and imprinted gene and repeat element methylation in the offspring

Am J Clin Nutr. 2013 Jan;97(1):94-9. doi: 10.3945/ajcn.112.042572. Epub 2012 Nov 14.

Abstract

Background: Epigenetic regulation of imprinted genes and transposable elements has been implicated in human disease and may be affected by maternal diet.

Objective: The objective was to determine the effect on offspring epigenetic status of nutritional and genetic factors that influence folate exposure in pregnancy.

Design: We measured folate intake from diet, the use of folic acid supplements and the period of consumption, maternal and cord red blood cell (RBC) folate, and genotypes for 5 methylation cycle enzymes in a prospective cohort study of pregnancies in the United Kingdom between 2000 and 2006. We related these to offspring methylation status within 3 maternally methylated imprinted genes: paternally expressed gene 3 (PEG3), insulin-like growth factor 2 (IGF2), and small nuclear ribonucleoprotein polypeptide N, and the long interspersed nuclear element 1 (LINE-1) in genomic DNA extracted from whole blood in 913 pregnancies.

Results: Supplement use after 12 wk of gestation was associated with a higher level of methylation in IGF2 (+0.7%; 95% CI: 0.02, 1.4; P = 0.044) and reduced methylation in both PEG3 (-0.5%; 95% CI: -0.9, -0.1; P = 0.018) and LINE-1 (-0.3%; 95% CI: -0.6, -0.04; P = 0.029). The same pattern was observed in relation to RBC folate in the cord blood at birth: IGF2 (P = 0.038), PEG3 (P < 0.001), and LINE-1 (P < 0.001). LINE-1 methylation was related to maternal RBC folate (P = 0.001) at 19 wk. No effect of supplement use up to 12 wk (current recommendation) was found.

Conclusions: Folic acid use after 12 wk of gestation influences offspring repeat element and imprinted gene methylation. We need to understand the consequences of these epigenetic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA / genetics
  • DNA Methylation
  • Diet
  • Dietary Supplements*
  • Female
  • Fetal Blood / chemistry
  • Folic Acid / administration & dosage*
  • Folic Acid / blood
  • Genome, Human
  • Genomic Imprinting*
  • Genotype
  • Humans
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Linear Models
  • Long Interspersed Nucleotide Elements / genetics
  • Maternal Nutritional Physiological Phenomena*
  • Multivariate Analysis
  • Neural Tube Defects / drug therapy
  • Neural Tube Defects / prevention & control
  • Pregnancy
  • Prospective Studies
  • Sequence Analysis, DNA
  • snRNP Core Proteins / genetics
  • snRNP Core Proteins / metabolism

Substances

  • IGF2 protein, human
  • Kruppel-Like Transcription Factors
  • PEG3 protein, human
  • SNRPN protein, human
  • snRNP Core Proteins
  • Insulin-Like Growth Factor II
  • DNA
  • Folic Acid