Assessment of candidate folate sensitive-differentially methylated regions in a randomised controlled trial of continued folic acid supplementation during the second and third trimesters of pregnancy

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#dna-methylation #dietary-supplements #female #folic-acid #hek293-cells

Assessment of candidate folate sensitive-differentially methylated regions in a randomised controlled trial of continued folic acid supplementation during the second and third trimesters of pregnancy

Harrison et al., 2019 | Ann Hum Genet | Rct

Citation

Harrison Alan, Pentieva Kristina, ... Parle-McDermott Anne. Assessment of candidate folate sensitive-differentially methylated regions in a randomised controlled trial of continued folic acid supplementation during the second and third trimesters of pregnancy. Ann Hum Genet. 2019-Jan;83(1):23-33. doi:10.1111/ahg.12281

Abstract

SCOPE: The aim of this study was to identify if specific regions of the human genome were sensitive to folate status by displaying changes in their DNA methylation patterns in response to continued folic acid supplementation during pregnancy. METHODS AND RESULTS: Samples (n = 119) from a previous randomised controlled trial in pregnancy were used to compare the DNA methylation profiles of the same woman pre- versus post-folic acid intervention. Candidate genes were identified from the literature and a pilot genome wide screen of six women (three from each of the folic acid and placebo arms of the trial). We did not observe consistent DNA methylation changes in response to folic acid intervention at any of our candidate genes (RASA4, DHFR, DHFR2, RASSF1A, EIF2C3, ATPF1). We did identify a 40% decrease in DNA methylation at the RASA4 promoter correlating with a 3.5-fold increase in its mRNA abundance in an in vitro cell culture model. CONCLUSION: Continued folic acid intervention over a 22-week period did not appear to significantly influence the DNA methylation status of six candidate genes in blood samples of women compared to placebo. However, DNA methylation may play a role in the gene expression control of the RASA4 gene.

Key Findings

Samples (n = 119) from a previous randomised controlled trial in pregnancy were used to compare the DNA methylation profiles of the same woman pre- versus post-folic acid intervention. Candidate genes were identified from the literature and a pilot genome wide screen of six women (three from each of the folic acid and placebo arms of the trial). We did not observe consistent DNA methylation changes in response to folic acid intervention at any of our candidate genes (RASA4, DHFR, DHFR2, RASSF1A,

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 119
Age Range See abstract
Condition See abstract

MeSH Terms

  • DNA Methylation
  • Dietary Supplements
  • Female
  • Folic Acid
  • HEK293 Cells
  • Humans
  • Pregnancy
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Promoter Regions, Genetic
  • ras GTPase-Activating Proteins

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
  • Vertical: folate-pregnancy

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09