1st Department of Pediatrics, Allergy and Cardiology, Wroclaw Medical University, Wroclaw, Poland.
Center for Experimental and Innovative Medicine, University of Agriculture in Krakow, Kraków, Poland.
Epigenetics. 2021 Jun;16(6):629-641. doi: 10.1080/15592294.2020.1814504. Epub 2020 Sep 9.
The increase in the prevalence of allergic diseases is believed to partially depend on environmental changes. DNA methylation is a major epigenetic mechanism, which is known to respond to environmental factors. A number of studies have revealed that patterns of DNA methylation may potentially predict allergic diseases.Here, we examined how maternal atopy is associated with methylation patterns in the cord blood of neonates.We conducted an epigenome-wide association study in a cohort of 96 mother-child pairs. Pregnant women aged not more than 35 years old, not currently smoking or exposed to environmental tobacco smoke, who did not report obesity before conception were considered eligible. They were further tested for atopy. Converted DNA from cord blood was analysed using Infinium MethylationEPIC; for statistical analysis, RnBeads software was applied. Gestational age and sex were included as covariates in the final analysis.83 DM sites were associated with maternal atopy. Within the top DM sites, there were CpG sites which mapped to genes SCD, ITM2C, NT5C3A and NPEPL1. Regional analysis revealed 25 tiling regions, 4 genes, 3 CpG islands and 5 gene promoters, (including PIGCP1, ADAM3A, ZSCAN12P1) associated with maternal atopy. Gene content analysis revealed pointwise enrichments in pathways related to purine-containing compound metabolism, the G1/S transition of the mitotic cell cycle, stem cell division and cellular glucose homoeostasis.These findings suggest that maternal atopy provides a unique intrauterine environment that may constitute the first environment in which exposure is associated with methylation patterns in newborn.
过敏疾病的流行率增加被认为部分取决于环境变化。DNA 甲基化是一种主要的表观遗传机制,已知其对环境因素有反应。许多研究表明,DNA 甲基化模式可能潜在地预测过敏疾病。在这里,我们研究了母体过敏与新生儿脐带血中甲基化模式的关系。我们在一个 96 对母婴队列中进行了全基因组关联研究。年龄不超过 35 岁的孕妇、当前不吸烟或不接触环境烟草烟雾、在受孕前不报告肥胖的孕妇被认为符合条件。她们进一步接受了过敏测试。使用 Infinium MethylationEPIC 分析脐带血中的转化 DNA;为了进行统计分析,应用了 RnBeads 软件。在最终分析中,将胎龄和性别作为协变量纳入。83 个 DM 位点与母体过敏有关。在顶级 DM 位点内,有 CpG 位点映射到 SCD、ITM2C、NT5C3A 和 NPEPL1 基因。区域分析显示 25 个平铺区域、4 个基因、3 个 CpG 岛和 5 个基因启动子(包括 PIGCP1、ADAM3A、ZSCAN12P1)与母体过敏有关。基因内容分析显示,与嘌呤化合物代谢、有丝分裂细胞周期的 G1/S 转换、干细胞分裂和细胞葡萄糖稳态相关的途径存在点状富集。这些发现表明,母体过敏提供了一个独特的宫内环境,可能构成暴露与新生儿甲基化模式相关的第一个环境。