Effects of Maternal High Folate and Low Vitamin B-12 on Dna Methylation in Cord Blood Mononuclear Cells

DNA methylation is an important epigenetic determinant in gene expression, with potential consequent effects on disease susceptibility. During embryogenesis, new DNA methylation patterns of the fetus are established, which renders this period highly susceptible to environmental modifiers. Maternal dietary intake of folate and vitamin B 12 has the potential to modulate DNA methylation via the provision of S‐adenosylmethionine. Maternal high folate and low B 12 status has been linked to an increased risk of obesity and insulin resistance in the offspring. Using a cohort from the PREnatal FOlic acid exposuRe on DNA Methylation in the newborn infant (PREFORM) study (n=291 mother‐child pairs), global (total 5‐methylcytosine [5mC] content) and gene‐specific DNA methylation in cord blood mononuclear cells between newborn infants born to mothers with high RBC folate (>2860 nmol/L) and low B 12 (<167 pmol/L) concentrations and controls born to mothers with lower RBC folate (<2860 nmol/L) and higher B 12 (>167 pmol/L) concentrations were investigated using liquid chromatography/mass spectrometry (LC/MS‐MS) and Illumina CpG methylation microarray, respectively. Infants from ‘high folate/low B 12 ’ mothers had 6.2% lower 5mC content than infants from ‘moderate folate/marginal to adequate B 12 ’ mothers (5.16±0.277 % vs. 5.50±0.411 %; p=0.0069). Furthermore, infants from ‘high folate/low B 12 ’ mothers were 9% heavier than infants from ‘moderate folate/marginal to adequate B 12 ’ mothers (3697±455 g vs. 3393±S451 g; p=0.001). These data suggest that maternal folate and B 12 status can influence global DNA methylation in the developing fetus and can potentially induce phenotypic changes in the newborn infant. Studies are underway to determine gene‐specific DNA methylation changes in cord blood mononuclear cells associated with maternal folate and B 12 status and their functional ramifications. Support or Funding Information Funded by: CIHR (MOP# 106446)