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

Alan Harrison, K. Pentieva, Mari Ozaki, H McNulty, Anne Parle-McDermott

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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.

Original languageEnglish
Pages (from-to)23-33
Number of pages11
JournalAnnals of Human Genetics
Issue number1
Early online date3 Sep 2018
Publication statusPublished - 1 Jan 2019



  • DNA
  • folic acid
  • gene expression
  • intervention
  • methylation

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