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

Paul Haggarty, Gwen Hoad, Doris M Campbell, Graham W Horgan, Chandrika Piyathilake, Geraldine McNeill

Research output: Contribution to journalArticle

67 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)94-99
Number of pages6
JournalThe American Journal of Clinical Nutrition
Volume97
Issue number1
Early online date14 Nov 2012
DOIs
Publication statusPublished - Jan 2013

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Folic Acid
Methylation
Pregnancy
Somatomedins
Genes
Epigenomics
Erythrocytes
Mothers
Fetal Blood
Nutrigenomics
Small Nuclear Ribonucleoproteins
Diet
DNA Transposable Elements
Cohort Studies
Genotype
Parturition
Prospective Studies
Peptides
DNA
Enzymes

Cite this

Folate in pregnancy and imprinted gene and repeat element methylation in the offspring. / Haggarty, Paul; Hoad, Gwen; Campbell, Doris M; Horgan, Graham W; Piyathilake, Chandrika; McNeill, Geraldine.

In: The American Journal of Clinical Nutrition, Vol. 97, No. 1, 01.2013, p. 94-99.

Research output: Contribution to journalArticle

Haggarty, Paul ; Hoad, Gwen ; Campbell, Doris M ; Horgan, Graham W ; Piyathilake, Chandrika ; McNeill, Geraldine. / Folate in pregnancy and imprinted gene and repeat element methylation in the offspring. In: The American Journal of Clinical Nutrition. 2013 ; Vol. 97, No. 1. pp. 94-99.
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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.",
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AU - Haggarty, Paul

AU - Hoad, Gwen

AU - Campbell, Doris M

AU - Horgan, Graham W

AU - Piyathilake, Chandrika

AU - McNeill, Geraldine

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N2 - 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.

AB - 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.

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DO - 10.3945/ajcn.112.042572

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SP - 94

EP - 99

JO - The American Journal of Clinical Nutrition

JF - The American Journal of Clinical Nutrition

SN - 0002-9165

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