Impact of folic acid intake during pregnancy on genomic imprinting of IGF2/H19 and 1-carbon metabolism

摘要

Folic acid is an essential component of 1-carbon metabolism, which generates methyl groups for DNA methylation. Disruption of genomic imprinting leads to biallelic expressionwhichmay affect disease susceptibility possibly reflected in high levels of S-adenosyl-homocysteine (SAH) and low levels of S-adenosyl-methionine (SAM). We investigated the association between folic acid supplementation during pregnancy and loss of imprinting (LOI) of IGF2 and H19 genes in placentas and cord blood of 90mother-child dyads in associationwith the methylenetetrahydrofolate reductase (MTHFR) genotype. Pyrosequencing was used to evaluate deviation from monoallelic expression among 47 placentas heterozygous for H19 and 37 placentas and cord blood tissues heterozygous for IGF2 and H19methylation levels of 48 placentas. We detected relaxation of imprinting (ROI) and LOI of H19 inplacentasnot associatedwithdifferences inmethylationlevels of theH19ICR. Placentas retainedmonoallelic allele-specific gene expression of IGF2, but 32.4 of cord blood samples displayed LOI of IGF2 and 10.8 showed ROI. High SAH levels were significantly associated with low H19 methylation. An interesting positive association between SAM/SAHratio and high H19methylation levelswasdetected among infantswith lowB(12) 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 IGF2/H19 and 1-carbon metabolism.