The nasal methylome as a biomarker of asthma and airway inflammation in children
The nasal methylome as a biomarker of asthma and airway inflammation in children
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鼻甲基组作为儿童哮喘和气道炎症的生物标志物
DOI：
10.1038/s41467-019-11058-3
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发表时间：
2019-07-12
影响因子：
16.6
通讯作者：
Gold, Diane R.
中科院分区：
文献类型：
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作者：
Cardenas, Andres;Sordillo, Joanne E.;Gold, Diane R.
鼻细胞表观基因组可作为气道疾病和环境反应的生物标志物。在这里，我们收集了547名儿童（平均年龄12.9岁）的前鼻孔的鼻拭子，并用Infinium MethylationEPIC Bead-Chip测量DNA甲基化（DNAm）。我们对当前哮喘、过敏原致敏、过敏性鼻炎、呼出气一氧化氮（FeNO）分数和肺功能进行鼻表观基因组全关联分析（EWAS）。我们发现了哮喘（285-CpG）、FeNO（8，372-CpG; 191-DMR）、总IgE（3-CpG; 3-DMR）、环境IgE（17-CpG; 4-DMR）、过敏性哮喘（1，235-CpG; 7-DMR）和支气管扩张剂反应（130-CpG）的多个差异甲基化CpG（FDR <0.05）和区域（DMR; >= 5-CpG和FDR < 0.05）。已发现DMR注释了与过敏性哮喘、Th 2活化和嗜酸性粒细胞增多症有关的基因（EPX、IL 4、IL 13）以及先前与哮喘和血液EWAS中IgE相关的基因（ACOT 7、SLC 25 A25）。哮喘、IgE和FeNO与鼻表观遗传年龄加速相关。鼻表观基因组是哮喘、过敏和气道炎症的敏感生物标志物。
The nasal cellular epigenome may serve as biomarker of airway disease and environmental response. Here we collect nasal swabs from the anterior nares of 547 children (mean-age 12.9 y), and measure DNA methylation (DNAm) with the Infinium MethylationEPIC Bead-Chip. We perform nasal Epigenome-Wide Association analyses (EWAS) of current asthma, allergen sensitization, allergic rhinitis, fractional exhaled nitric oxide (FeNO) and lung function. We find multiple differentially methylated CpGs (FDR < 0.05) and Regions (DMRs; >= 5-CpGs and FDR < 0.05) for asthma (285-CpGs), FeNO (8,372-CpGs; 191-DMRs), total IgE (3-CpGs; 3-DMRs), environment IgE (17-CpGs; 4-DMRs), allergic asthma (1,235-CpGs; 7-DMRs) and bronchodilator response (130-CpGs). Discovered DMRs annotated to genes implicated in allergic asthma, Th2 activation and eosinophilia (EPX, IL4, IL13) and genes previously associated with asthma and IgE in EWAS of blood (ACOT7, SLC25A25). Asthma, IgE and FeNO were associated with nasal epigenetic age acceleration. The nasal epigenome is a sensitive biomarker of asthma, allergy and airway inflammation.