Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 566-575 |
| Number of pages | 10 |
| Journal | American Journal of Clinical Nutrition |
| Volume | 107 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 9 Apr 2018 |
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Keywords
- folic acid
- pregnancy
- DNA methylation
- epigenetics
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Gene-specific DNA methylation in newborns in response to folic acid supplementation during the second and third trimesters of pregnancy : epigenetic analysis from a randomized controlled trial. / Caffrey, Aoife; Irwin, Rachelle E; McNulty, Helene; Strain, JJ; Lees Murdock, Diane; McNulty, Briege; Ward, Mary; Walsh, Colum; Pentieva, Kristina.
In: American Journal of Clinical Nutrition, Vol. 107, No. 4, 09.04.2018, p. 566-575.Research output: Contribution to journal › Article
TY - JOUR
T1 - Gene-specific DNA methylation in newborns in response to folic acid supplementation during the second and third trimesters of pregnancy
T2 - epigenetic analysis from a randomized controlled trial
AU - Caffrey, Aoife
AU - Irwin, Rachelle E
AU - McNulty, Helene
AU - Strain, JJ
AU - Lees Murdock, Diane
AU - McNulty, Briege
AU - Ward, Mary
AU - Walsh, Colum
AU - Pentieva, Kristina
N1 - UIR non-compliant due to manuscript not being uploaded within 3 months of accepted date, but the manuscript with uploaded within days of the publication date so is compliant
PY - 2018/4/9
Y1 - 2018/4/9
N2 - Background: Emerging evidence suggests that maternal folate status can impact cognitive development in childhood. Folate-dependent DNA methylation may provide a biological mechanism to link folate status during pregnancy with cognition in the offspring. Objective: The objective was to investigate the effect of continued folic acid (FA) supplementation beyond the first trimester of pregnancy on DNA methylation in cord blood of epigenetically-controlled genes related to brain development and function. Design: Using available cord blood samples (n = 86) from the Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) trial in pregnancy, we applied pyrosequencing techniques to analyze cord blood DNA at nine candidate loci known to be regulated by methylation including some previously implicated in observational studies: the widely-dispersed retrotransposon LINE-1 and eight single-copy loci (RBM46, PEG3, IGF2, GRB10, BDNF, GRIN3B, OPCML and APC2). Results: The newborns of mothers who received FA (400 µg/d) during pregnancy, compared to placebo, had significantly lower overall DNA methylation levels at LINE-1 (57.2 ± 2.1 % vs 56.3 ± 1.7 %; P = 0.024), IGF2 (51.2 ± 5.1 % vs 48.9 ± 4.4 %; P = 0.021) and BDNF (3.1 ± 0.8 % vs 2.7 ± 0.7 %; P = 0.003). The effect of FA treatment on DNA methylation was significant only in female offspring for IGF2 (P = 0.028) and only in males for BDNF (P = 0.012). For GRB10 and GRIN3B, we detected no effect on overall methylation, however, individual CpG sites showed significant DNA methylation changes in response to FA. Conclusions: Continued supplementation with FA through trimesters 2 and 3 of pregnancy results in significant changes in DNA methylation in cord blood of genes related to brain development. The findings offer a potential biological mechanism linking maternal folate status with neurodevelopment of the offspring, but this requires further investigation using a genome-wide approach.
AB - Background: Emerging evidence suggests that maternal folate status can impact cognitive development in childhood. Folate-dependent DNA methylation may provide a biological mechanism to link folate status during pregnancy with cognition in the offspring. Objective: The objective was to investigate the effect of continued folic acid (FA) supplementation beyond the first trimester of pregnancy on DNA methylation in cord blood of epigenetically-controlled genes related to brain development and function. Design: Using available cord blood samples (n = 86) from the Folic Acid Supplementation in the Second and Third Trimesters (FASSTT) trial in pregnancy, we applied pyrosequencing techniques to analyze cord blood DNA at nine candidate loci known to be regulated by methylation including some previously implicated in observational studies: the widely-dispersed retrotransposon LINE-1 and eight single-copy loci (RBM46, PEG3, IGF2, GRB10, BDNF, GRIN3B, OPCML and APC2). Results: The newborns of mothers who received FA (400 µg/d) during pregnancy, compared to placebo, had significantly lower overall DNA methylation levels at LINE-1 (57.2 ± 2.1 % vs 56.3 ± 1.7 %; P = 0.024), IGF2 (51.2 ± 5.1 % vs 48.9 ± 4.4 %; P = 0.021) and BDNF (3.1 ± 0.8 % vs 2.7 ± 0.7 %; P = 0.003). The effect of FA treatment on DNA methylation was significant only in female offspring for IGF2 (P = 0.028) and only in males for BDNF (P = 0.012). For GRB10 and GRIN3B, we detected no effect on overall methylation, however, individual CpG sites showed significant DNA methylation changes in response to FA. Conclusions: Continued supplementation with FA through trimesters 2 and 3 of pregnancy results in significant changes in DNA methylation in cord blood of genes related to brain development. The findings offer a potential biological mechanism linking maternal folate status with neurodevelopment of the offspring, but this requires further investigation using a genome-wide approach.
KW - folic acid
KW - pregnancy
KW - DNA methylation
KW - epigenetics
U2 - 10.1093/ajcn/nqx069
DO - 10.1093/ajcn/nqx069
M3 - Article
C2 - 29635492
VL - 107
SP - 566
EP - 575
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
SN - 0002-9165
IS - 4
ER -