title: Folate in pregnancy and imprinted gene and repeat element methylation in the offspring.
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.
  
  
  METHODS
  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.
authors.affiliation: Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom. p.haggarty@abdn.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Haggarty
authors.forename: Gwen
authors.initials: G
authors.lastname: Hoad
authors.forename: Doris M
authors.initials: DM
authors.lastname: Campbell
authors.forename: Graham W
authors.initials: GW
authors.lastname: Horgan
authors.forename: Chandrika
authors.initials: C
authors.lastname: Piyathilake
authors.forename: Geraldine
authors.initials: G
authors.lastname: McNeill
mesh_terms: D000328:Adult; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D004032:Diet; D019587:Dietary Supplements; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D015894:Genome, Human; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D016014:Linear Models; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D039382:Maternal Nutritional Physiological Phenomena; D015999:Multivariate Analysis; D009436:Neural Tube Defects / Q000188:drug therapy / Q000517:prevention & control; D011247:Pregnancy; D011446:Prospective Studies; D017422:Sequence Analysis, DNA; D055517:snRNP Core Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C035170:IGF2 protein, human; D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; C526417:SNRPN protein, human; D055517:snRNP Core Proteins; D007335:Insulin-Like Growth Factor II; D004247:DNA; D005492:Folic Acid