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Association Between One‐carbon Metabolism Indices and DNA Methylation Status in Maternal and Cord Blood
Author(s) -
Park Hea Jin,
Knight Anna K,
Fleming Jennifer M,
Hausman Dorothy B,
Caudill Marie A,
Malysheva Olga V,
Kauwell Gail PA,
Sokolow Andrew,
Fisher Susan,
Smith Alicia K,
Bailey Lynn B
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.802.28
Subject(s) - cord blood , dna methylation , cpg site , choline , methylation , umbilical cord , homocysteine , whole blood , pregnancy , epigenetics , metabolism , medicine , endocrinology , andrology , chemistry , biology , biochemistry , immunology , dna , genetics , gene expression , gene
One‐carbon metabolism is a crucial component of metabolism in all cells and tissues supporting DNA methylation and DNA synthesis. It is critically important during pregnancy to ensure normal cell division and growth of fetal and maternal tissues; however, the impact of one‐carbon metabolism indices during pregnancy on DNA methylation has not been investigated. In this study, status of one‐carbon metabolism indices and DNA methylation in maternal blood and cord blood were measured. One‐carbon metabolism indices included serum folate, red blood cell folate, plasma folic acid, plasma 5‐methyltetrahydrofolate (5MTHF), plasma methionine, plasma choline and choline metabolites (dimethylglycine (DMG), betaine, trimethylamine N ‐oxide), plasma homocysteine, plasma SAM, SAH and the ratio of SAM/SAH and plasma vitamin B 12 . Healthy pregnant women (n=28) were recruited at a local midwifery clinic (Athens Regional Midwifery Clinic, Athens, GA), and maternal blood was collected at baseline (<12wk gestation) and delivery. Umbilical cord blood from the mothers was also collected at delivery. DNA methylation in maternal and cord blood were measured across > 485,000 CpG sites using the Infinium Human Methylation 450 BeadChip. Using a linear mixed‐effects model, we examined the relationship between DNA methylation of each CpG site and gestational week to determine CpG sites that change over pregnancy in maternal blood. We identified 993 such CpG sites (FDR<.05), which were then interrogated for associations with one‐carbon metabolism indices. In maternal blood, a CpG site was associated with DMG levels after multiple test correction. Interestingly, in cord blood, methylation of three CpG sites was negatively associated with 5MTHF level (FDR<.05). These CpG sites were annotated to Myc‐associated Zinc finger protein ( MAZ ), discs large homolog 2 ( DLG2 ), and paraneoplastic Ma antigen ( PNMA1 ), which have previously been associated with cancer progression and neurological function. Results suggest a unique association between one‐carbon metabolism indices and methylation status of specific CpG sites in cord blood. Future research should address changes in methylation of these genes in studies of brain development and neural tube defects. Support or Funding Information Support provided by Georgia Experimental Agricultural Station, HATCH #GEO00706 and #GEO00707, Obesity Initiative at the University of Georgia (UGA) and UGA Office of Vice President for Research.