ABSTRACT

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.

摘要

过敏性疾病患病率的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，已知它会对环境因素做出反应。许多研究表明 DNA 甲基化模式可能预测过敏性疾病。

在这里，我们研究了母体特应性如何与新生儿脐带血甲基化模式相关。

我们对 96 对母子进行了一项全表观基因组关联研究。年龄不超过35岁、目前不吸烟或暴露于环境烟草烟雾、受孕前未报告肥胖的孕妇被视为符合资格。他们进一步接受了特应性测试。使用 Infinium MmethylationEPIC 分析脐带血转化的 DNA；应用RnBeads软件进行统计分析。孕龄和性别作为最终分析中的协变量。

83 个 DM 部位与母亲特应性相关。在顶部 DM 位点内，有 CpG 位点映射到基因 SCD、ITM2C、NT5C3A 和 NPEPL1。区域分析揭示了与母体特应性相关的 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）。基因内容分析揭示了与含嘌呤化合物代谢、有丝分裂细胞周期的 G1/S 转变、干细胞分裂和细胞葡萄糖稳态相关的途径的逐点富集。

这些发现表明，母体特应性提供了独特的宫内环境，可能构成暴露与新生儿甲基化模式相关的第一个环境。