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胎盘基甲基化和出生体重之间的关联

Michael Mortillo¹, Elizabeth Kennedy¹, Karen Hermetz¹

¹Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University.

Epigenetics reports

|August 2, 2024

概括

这项研究研究了胎盘5-基甲基细胞素 (5hmC) 和它与新生儿出生体重的关联. 虽然CUBN基因中的一个CpG位点显示出显著的联系,但总体而言,胎盘5hmC没有显示出广泛的出生体重关联.

科学领域:

表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.
发展生物学发展生物学
基因组学就是基因组学.

背景情况:

5-基甲基细胞因子 (5hmC) 是5-甲基细胞因子 (5mC) 的氧化衍生物,主要被认为是DNA脱甲基化中间体.
新出现的证据表明,5hmC可能具有除去甲基化之外的独立功能作用.
胎盘表观遗传学,包括DNA甲基化和基甲基化,对于胎儿发育和出生体重的结果至关重要.

研究的目的:

进行一个全表观基因组关联研究 (EWAS),研究胎盘5-基甲基细胞素 (5hmC) 与新生儿出生体重之间的关系.
评估5hmC信号对传统的全表观基因组研究的影响,这些研究仅依赖于二硫酸盐 (BS) 修饰 (测量5mC和5hmC).
确定5hmC是否在调节出生体重方面发挥着重要且独立的作用.

主要方法:

从胎盘样本中提取的DNA的并行双硫酸盐和氧化双硫酸盐修饰.
基于阵列的评估用于量化整个表观基因组的5hmC和5mC水平.
全表观基因组关联研究 (EWAS) 分析,将胎盘5hmC/5mC水平与罗德岛儿童健康研究 (RICHS) 的新生儿出生体重数据相关联.
使用组合的5hmC+5mC数据与仅使用5mC数据对EWAS结果的比较分析.

主要成果:

在CUBN基因中的特定CpG位点的5hmC与新生儿出生体重 (错误发现率<0.05) 之间发现了显著的关联.
还发现,CUBN基因的表达与出生体重有关,这表明存在功能联系.
在使用组合5hmC+5mC和仅5mC评估的EWAS效应估计之间观察到强烈的正相关性 (r = 0.77,p < 0.0001).
没有发现胎盘5hmC与出生体重之间的广泛关联,这表明5hmC可能不是出生体重变化的主要驱动因素.

结论:

仅使用双硫酸盐修饰的传统全基因组研究可以准确地评估CpG特异性DNA甲基化与出生体重相关的EWAS.
虽然CUBN中的特定5hmC位点与出生体重有关,但胎盘5hmC对出生体重变化的总体贡献似乎有限.
这些发现表明,标准的5mC评估在很大程度上足以检测甲基化相关的出生体重影响,但5hmC的功能作用需要进一步研究.

关键词:

出生时的体重出生时的体重.全表观基因组协会研究研究.氧甲基化氧甲基化胎盘胎盘胎盘胎盘

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