Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

母体及脐血中一碳代谢指标与DNA甲基化状态的关联

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作者:Anna K Knight, Hea Jin Park, Dorothy B Hausman, Jennifer M Fleming, Victoria L Bland, Gisselle Rosa, Elizabeth M Kennedy, Marie A Caudill, Olga Malysheva, Gail P A Kauwell, Andrew Sokolow, Susan Fisher, Alicia K Smith, Lynn B Bailey

Abstract

One-carbon metabolism is essential for multiple cellular processes and can be assessed by the concentration of folate metabolites in the blood. One-carbon metabolites serve as methyl donors that are required for epigenetic regulation. Deficiencies in these metabolites are associated with a variety of poor health outcomes, including adverse pregnancy complications. DNA methylation is known to vary with one-carbon metabolite concentration, and therefore may modulate the risk of adverse pregnancy outcomes. This study addresses changes in one-carbon indices over pregnancy and the relationship between maternal and child DNA methylation and metabolite concentrations by leveraging data from 24 mother-infant dyads. Five of the 13 metabolites measured from maternal blood and methylation levels of 993 CpG sites changed over the course of pregnancy. In dyads, maternal and fetal one-carbon concentrations were highly correlated, both early in pregnancy and at delivery. The 993 CpG sites whose methylation levels changed over pregnancy in maternal blood were also investigated for associations with metabolite concentrations in infant blood at delivery, where five CpG sites were associated with the concentration of at least one metabolite. Identification of CpG sites that change over pregnancy may result in better characterization of genes and pathways involved in maintaining a healthy, term pregnancy.

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