DNA甲基化差异通过标准化胎儿/胎盘重量比分层提示先天性心脏病新生儿神经发育缺陷。

IF 2.6 3区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
PLoS ONE Pub Date : 2025-08-06 eCollection Date: 2025-01-01 DOI:10.1371/journal.pone.0317944
Marin Jacobwitz, Michael Xie, Jamie Catalano, Ingo Helbig, J William Gaynor, Nancy Burnham, Rebecca L Linn, Juliana Gebb, Mark W Russell, Hakon Hakonarson, Barbara H Chaiyachati, Ana G Cristancho
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引用次数: 0

摘要

背景:我们缺乏预测先天性心脏病(CHD)患儿神经发育(ND)结局的早期生物标志物。CHD胎儿的胎盘有异常,包括胎儿/胎盘重量比(F/P)不平衡。尽管DNA甲基化谱揭示了母胎环境(MFE)的一些见解,但尚不清楚DNA甲基化是否与标准化F/P体重比组相关,以及这些差异如何与ND结局相关。方法:我们前瞻性地招募了一组携带冠心病胎儿的孕妇。该队列的一个子集对脐带血或产后血液(45个足月新生儿)进行了DNA甲基化。我们计算了归一化F/P权重比,重点分析了三个归一化F/P比率组。我们计算了八个ND残疾相关基因组的差异甲基化信号。将标准化F/P比率与18个月Bayley婴儿发育量表iii评分(BSID-III)进行比较。结果:差异甲基化区域的无偏基因本体富集分析揭示了大脑发育相关通路的富集。虽然标准化F/P重量比组与BSID-III组之间无显著差异,但疾病相关基因集通路分析显示,最严重失衡F/P重量比组与正常F/P重量比组之间的甲基化差异显著。结论:差异甲基化区基因本体富集分析显示,归一化F/P权重比组间神经发生基因存在显著差异。此外,我们的数据还发现,与老龄冠心病人群中常见的ND功能障碍相关的基因通路中,不平衡和平衡标准化F/P重量比组的甲基化差异表明,ND疾病的趋同通路应该进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DNA methylation differences stratified by normalized fetal/placental weight ratios suggest neurodevelopmental deficits in neonates with congenital heart disease.

Background: We lack early biomarkers for predicting neurodevelopment (ND) outcomes in children with congenital heart disease (CHD). Placentas of fetuses with CHD have abnormalities, including unbalanced fetal/placental weight ratios (F/P). Although DNA methylation profiles have revealed insights into the maternal-fetal environment (MFE), it is unknown if DNA methylation correlates to normalized F/P weight ratio groups and how these differences relate to ND outcomes.

Methods: We prospectively recruited a cohort of pregnant women carrying a fetus with CHD. A subset of the cohort had DNA methylation performed on either umbilical cord blood or postnatal blood (45 full-term neonates). We calculated normalized F/P weight ratios, focusing on three normalized F/P ratio groups for analysis. We calculated differential methylation signals in eight ND disabilities-associated gene sets. Normalized F/P ratios were compared to 18-month Bayley Scales of Infant Development-III scores (BSID-III).

Results: Unbiased gene ontology enrichment analysis of differentially methylated regions revealed enrichment for brain development-related pathways. Although there were no significant differences between normalized F/P weight ratio groups and BSID-III, disease-associated gene set pathway analysis revealed significant methylation differences between the most severely unbalanced F/P weight ratio and normal F/P weight ratio groups.

Conclusion: Gene ontology enrichment analysis of differential methylation regions revealed significant differences between normalized F/P weight ratio groups in neurogenesis genes. Furthermore, our data identified methylation differences between unbalanced and balanced normalized F/P weight ratio groups in gene pathways associated with ND dysfunction common in the aging CHD population suggesting converging pathways for ND disorders that should be investigated further.

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来源期刊
PLoS ONE
PLoS ONE 生物-生物学
CiteScore
6.20
自引率
5.40%
发文量
14242
审稿时长
3.7 months
期刊介绍: PLOS ONE is an international, peer-reviewed, open-access, online publication. PLOS ONE welcomes reports on primary research from any scientific discipline. It provides: * Open-access—freely accessible online, authors retain copyright * Fast publication times * Peer review by expert, practicing researchers * Post-publication tools to indicate quality and impact * Community-based dialogue on articles * Worldwide media coverage
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