Impact of Folic Acid Intake During Pregnancy on Genomic Imprinting of and 1-carbon Metabolism

Folic acid is an essential component of 1-carbon metabolism, which generates methyl groups for DNA methylation. Disruption of genomic imprinting leads to biallelic expression which may affect disease susceptibility possibly reflected in high levels of -adenosyl-homocysteine (SAH) and low levels of -adenosyl-methionine (SAM). We investigated the association between folic acid supplementation during pregnancy and loss of imprinting (LOI) of and genes in placentas and cord blood of 90 mother-child dyads in association with the methylenetetrahydrofolate reductase () genotype. Pyrosequencing was used to evaluate deviation from monoallelic expression among 47 placentas heterozygous for and 37 placentas and cord blood tissues heterozygous for and methylation levels of 48 placentas. We detected relaxation of imprinting (ROI) and LOI of in placentas not associated with differences in methylation levels of the H19ICR. Placentas retained monoallelic allele-specific gene expression of , but 32.4% of cord blood samples displayed LOI of and 10.8% showed ROI. High SAH levels were significantly associated with low methylation. An interesting positive association between SAM/SAH ratio and high methylation levels was detected among infants with low B levels. Our data suggest profound differences in regulation of imprinting in placenta and cord blood; a lack of correlation of the methylome, transcriptome, and proteome; and a complex regulatory feedback network between free methyl groups and genomic imprinting at birth.-Tserga, A., Binder, A. M., Michels, K. B. Impact of folic acid intake during pregnancy on genomic imprinting of and 1-carbon metabolism.