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母亲和脐带血中一碳代谢指标与 DNA 甲基化状态的关联。

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

机构信息

Genetics and Molecular Biology Program, Emory University, Atlanta, GA, USA.

Department of Foods and Nutrition, University of Georgia, Athens, GA, USA.

出版信息

Sci Rep. 2018 Nov 15;8(1):16873. doi: 10.1038/s41598-018-35111-1.

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.

摘要

一碳代谢对于多种细胞过程至关重要,可以通过血液中叶酸代谢物的浓度来评估。一碳代谢物作为甲基供体,是表观遗传调控所必需的。这些代谢物的缺乏与多种健康不良后果相关,包括不良的妊娠并发症。已知 DNA 甲基化随一碳代谢物浓度的变化而变化,因此可能调节不良妊娠结局的风险。本研究通过利用 24 对母婴对的数据,探讨了妊娠过程中一碳指标的变化以及母婴 DNA 甲基化和代谢物浓度之间的关系。从母体血液中测量的 13 种代谢物中的 5 种以及 993 个 CpG 位点的甲基化水平在整个妊娠过程中发生了变化。在母婴对中,母体和胎儿的一碳浓度在妊娠早期和分娩时高度相关。在母体血液中,993 个 CpG 位点的甲基化水平在妊娠期间发生了变化,这些 CpG 位点也与婴儿血液中至少一种代谢物的浓度相关,其中 5 个 CpG 位点与至少一种代谢物的浓度相关。鉴定出在妊娠期间发生变化的 CpG 位点,可能有助于更好地描述参与维持健康足月妊娠的基因和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/65ae/6237996/39ae845e7ffa/41598_2018_35111_Fig1_HTML.jpg

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