Effects of Maternal High Folate and Low Vitamin B12 on DNA Methylation in Cord Blood Mononuclear Cells

Abstract

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 B12 has the potential to modulate DNA methylation via the provision of S‐adenosylmethionine. Maternal high folate and low B12 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 B12 (<167 pmol/L) concentrations and controls born to mothers with lower RBC folate (<2860 nmol/L) and higher B12 (>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 B12’ mothers had 6.2% lower 5mC content than infants from ‘moderate folate/marginal to adequate B12’ mothers (5.16±0.277 % vs. 5.50±0.411 %; p=0.0069). Furthermore, infants from ‘high folate/low B12’ mothers were 9% heavier than infants from ‘moderate folate/marginal to adequate B12’ mothers (3697±455 g vs. 3393±S451 g; p=0.001). These data suggest that maternal folate and B12 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 B12 status and their functional ramifications.Support or Funding InformationFunded by: CIHR (MOP# 106446)