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孕期低血糖指数饮食可诱导新生儿血液中 DNA 甲基化的变化:来自 ROLO 随机对照试验的结果。

A Low Glycaemic Index Diet in Pregnancy Induces DNA Methylation Variation in Blood of Newborns: Results from the ROLO Randomised Controlled Trial.

机构信息

UCD Perinatal Research Centre, Obstetrics and Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital, Dublin 2, Ireland.

Cancer and Disease Epigenetics, Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia.

出版信息

Nutrients. 2018 Apr 6;10(4):455. doi: 10.3390/nu10040455.

DOI:10.3390/nu10040455
PMID:29642382
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5946240/
Abstract

The epigenetic profile of the developing fetus is sensitive to environmental influence. Maternal diet has been shown to influence DNA methylation patterns in offspring, but research in humans is limited. We investigated the impact of a low glycaemic index dietary intervention during pregnancy on offspring DNA methylation patterns using a genome-wide methylation approach. Sixty neonates were selected from the ROLO (Randomised cOntrol trial of LOw glycaemic index diet to prevent macrosomia) study: 30 neonates from the low glycaemic index intervention arm and 30 from the control, whose mothers received no specific dietary advice. DNA methylation was investigated in 771,484 CpG sites in free DNA from cord blood serum. Principal component analysis and linear regression were carried out comparing the intervention and control groups. Gene clustering and pathway analysis were also explored. Widespread variation was identified in the newborns exposed to the dietary intervention, accounting for 11% of the total level of DNA methylation variation within the dataset. No association was found with maternal early-pregnancy body mass index (BMI), infant sex, or birthweight. Pathway analysis identified common influences of the intervention on gene clusters plausibly linked to pathways targeted by the intervention, including cardiac and immune functioning. Analysis in 60 additional samples from the ROLO study failed to replicate the original findings. Using a modest-sized discovery sample, we identified preliminary evidence of differential methylation in progeny of mothers exposed to a dietary intervention during pregnancy.

摘要

胎儿发育的表观遗传特征对外界环境影响敏感。母亲的饮食已被证明会影响后代的 DNA 甲基化模式,但人类的研究有限。我们使用全基因组甲基化方法研究了孕期低升糖指数饮食干预对后代 DNA 甲基化模式的影响。从 ROLO(低升糖指数饮食预防巨大儿的随机对照试验)研究中选择了 60 名新生儿:30 名来自低升糖指数干预组,30 名来自对照组,对照组母亲未接受任何特定的饮食建议。在脐带血清游离 DNA 中检测了 771,484 个 CpG 位点的 DNA 甲基化。比较了干预组和对照组,进行了主成分分析和线性回归。还探索了基因聚类和途径分析。暴露于饮食干预的新生儿存在广泛的变化,占数据集内总 DNA 甲基化变化的 11%。与母亲孕早期的体重指数(BMI)、婴儿性别或出生体重无关。途径分析确定了干预对基因簇的共同影响,这些基因簇可能与干预的途径有关,包括心脏和免疫功能。在 ROLO 研究中的 60 个额外样本中的分析未能复制原始发现。使用适度大小的发现样本,我们在暴露于孕期饮食干预的母亲的后代中发现了初步的差异甲基化证据。

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