The groundbreaking work performed by a team of UK scientists found modifications in genes crucial in early development may be linked to levels of homocysteine – an amino acid in the blood that can be broken down by folic acid – of newborn babies.
“It has been known for many years that folic acid supplementation is essential for women during pregnancy to reduce the risk of neural tube defects and low birth weight delivery. However, we had little idea as to how this worked. This study is the first to suggest that methylation of particular genes in the baby’s DNA may be the key to unlocking the secret of the action of folic acid,” said William Farrell, Professor of Human Genomics, at the University of Keele – senior author of the new research.
DNA methylation is important in regulating cell growth and differentiation and can serve many important biological purposes, including suppressing gene expression of potentially harmful information that is present in the human genome.
It has been suggested that folic acid, though its metabolism of chemicals like homocysteine, might achieve its clinical benefits through DNA methylation – a chemical modification where a methyl group is added to a stretch of DNA that codes for a gene.
Homocysteine levels in the blood are strongly influenced by both dietary and genetic factors, with dietary folic acid and vitamins B-6 and B-12 having the greatest effects. Several studies found that higher blood levels of B vitamins are related, at least in part, to lower concentrations of homocysteine.
B for baby benefits
An overwhelming body of evidence links folate deficiency in early pregnancy to increased risk of neural tube defects – most commonly spina bifida and anencephaly – in infants. Folic acid supplementation has also been shown to protect against low birth weight.
This connection led to the 1998 introduction of public health measures in the U.S. and Canada, where all grain products are fortified with folic acid. A total of 51 countries now have some degree of mandatory fortification of flour with folic acid.
The new study examined the relationship between folic acid – the synthetic, bioavailable form of the B vitamin folate – and its metabolites on DNA methylation in human blood from the umbilical cord, using state-of-the-art techniques which simultaneously examine modifications at more than 27,000 sites in the DNA, that are associated with more than 14,000 genes.
The authors reported that unbiased analysis of DNA methylation “revealed a significant correlation of DNA modification patterns with plasma homocysteine levels, and birth weight.”
“These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome,” said the researchers.
They concluded that their genome-wide interrogation had identified gene-specific patterns associated with plasma homocysteine concentration, DNA methylation levels, and birth weight.
“Our initial data highlight the importance of changes within these regulatory regions that, while requiring further investigation, may uncover genes important in fetal development,” said Farrell and colleagues.
Published online ahead of print, doi: 10.4161/epi.6.1.13392
“Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans”
Authors: A.A. Fryer, R.D. Emes, K.M.K. Ismail, K.E. Haworth, C. Mein, W.D. Carroll, W.E. Farrell