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母亲患有妊娠糖尿病的新生儿的表观遗传变化可能与新生儿低血糖有关。

Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia.

机构信息

Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.

Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, Tokyo, Japan.

出版信息

Front Endocrinol (Lausanne). 2021 Jun 29;12:690648. doi: 10.3389/fendo.2021.690648. eCollection 2021.

Abstract

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

摘要

与新生儿低血糖相关的表观遗传变化的检测可能揭示发病机制,并预测后代未来疾病的发生。我们假设新生儿低血糖反映了与母体妊娠期糖尿病相关的环境。本研究旨在确定与新生儿低血糖相关的表观遗传变化。通过稳健线性回归分析,研究了来自患有良好控制的妊娠期糖尿病的母亲的 128 名足月出生的后代中,出生后 1 小时新生儿血浆葡萄糖 (PG) 水平与使用 Infinium HumanMethylation EPIC BeadChip 进行的 DNA 甲基化之间的关联。在向回归模型中添加婴儿性别、分娩方式、胎龄和血细胞成分作为协变量后,脐带血中 12 个 CpG 位点的 DNA 甲基化与出生后 1 小时的 PG 水平显著相关。位于 替代转录起始位点附近的两个 CpG 位点的 DNA 甲基化与出生后 1 小时的 PG 水平显著相关(经错误发现率调整的 < 0.05)。这些位点的甲基化水平随着新生儿出生后 1 小时 PG 水平的降低而升高。总之,妊娠期糖尿病与脐带血细胞中 替代转录起始位点的 DNA 甲基化变化有关。这是第一个与新生儿出生后 1 小时 PG 相关的 DNA 甲基化变化的报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d28/8276691/05c6c4cd408f/fendo-12-690648-g001.jpg

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