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

• Published in: The American journal of clinical nutrition Vol. 97; no. 1; pp. 94 - 99
• Main Authors: Haggarty, Paul, Hoad, Gwen, Campbell, Doris M, Horgan, Graham W, Piyathilake, Chandrika, McNeill, Geraldine
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 2013; American Society for Nutrition; American Society for Clinical Nutrition, Inc
• Subjects: Adult; Biological and medical sciences; clinical nutrition; cohort studies; Diet; Dietary Supplements; DNA; DNA - genetics; DNA Methylation; enzymes; Epigenetics; erythrocytes; Feeding. Feeding behavior; Female; Fetal Blood - chemistry; folic acid; Folic Acid - administration & dosage; Folic Acid - blood; Fundamental and applied biological sciences. Psychology; Gene expression; genes; Genome, Human; Genomic Imprinting; Genotype; Genotype & phenotype; human diseases; Humans; insulin-like growth factor II; 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; methylation; Multivariate Analysis; Neural Tube Defects - drug therapy; Neural Tube Defects - prevention & control; nutritional status; polypeptides; Pregnancy; progeny; Prospective Studies; Sequence Analysis, DNA; snRNP Core Proteins - genetics; snRNP Core Proteins - metabolism; transposons; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B; United Kingdom; United Kingdom > UK; Micronutrient; Pregnancy; Gene; Methylation; Folic acid; Folate
• ISSN: 0002-9165; 1938-3207
• DOI: 10.3945/ajcn.112.042572

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.