Background

Epigenetic signatures in the nasal epithelium, which is a primary interface with the environment and an accessible proxy for the bronchial epithelium, might provide insights into mechanisms of allergic disease.

Objective

We aimed to identify and interpret methylation signatures in nasal epithelial brushes associated with rhinitis and asthma.

Methods

Nasal epithelial brushes were obtained from 455 children at the 16-year follow-up of the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study. Epigenome-wide association studies were performed on children with asthma, rhinitis, and asthma and/or rhinitis (AsRh) by using logistic regression, and the top results were replicated in 2 independent cohorts of African American and Puerto Rican children. Significant CpG sites were related to environmental exposures (pets, active and passive smoking, and molds) during secondary school and were correlated with gene expression by RNA-sequencing (n = 244).

Results

The epigenome-wide association studies identified CpG sites significantly associated with rhinitis (n = 81) and AsRh (n = 75), but not with asthma. We significantly replicated 62 of 81 CpG sites with rhinitis and 60 of 75 with AsRh, as well as 1 CpG site with asthma. Methylation of cg03565274 was negatively associated with AsRh and positively associated with exposure to pets during secondary school. DNA methylation signals associated with AsRh were mainly driven by specific IgE–positive subjects. DNA methylation related to gene transcripts that were enriched for immune pathways and expressed in immune and epithelial cells. Nasal CpG sites performed well in predicting AsRh.

Conclusions

We identified replicable DNA methylation profiles of asthma and rhinitis in nasal brushes. Exposure to pets may affect nasal epithelial methylation in relation to asthma and rhinitis.

中文翻译：

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哮喘和鼻炎的鼻DNA甲基化分析。

背景

鼻上皮中的表观遗传学标志是与环境的主要界面，是支气管上皮的可及代理，它可能为过敏性疾病的机理提供见解。

目的

我们旨在识别和解释与鼻炎和哮喘相关的鼻上皮刷中的甲基化特征。

方法

在对荷兰哮喘和螨虫过敏的出生队列进行的16年随访中，从455名儿童中获得了鼻上皮刷。使用logistic回归对哮喘，鼻炎和哮喘和/或鼻炎（AsRh）患儿进行了表观基因组关联研究，并在2个独立的非裔美国人和波多黎各儿童中复制了最高结果。CpG的重要位点与中学时期的环境暴露（宠物，主动和被动吸烟以及霉菌）有关，并通过RNA测序与基因表达相关（n = 244）。

结果

整个表观基因组关联研究确定了与鼻炎（n = 81）和AsRh（n = 75）显着相关的CpG位点，但与哮喘无关。我们显着复制了81个鼻炎CpG位点中的62个，使用AsRh复制了75个CpG位点中的60个，哮喘时复制了1个CpG位点。在中学期间，cg03565274的甲基化与AsRh呈负相关，而与宠物的暴露呈正相关。与AsRh相关的DNA甲基化信号主要由特定的IgE阳性受试者驱动。DNA甲基化与基因转录物有关，这些转录物富含免疫途径并在免疫和上皮细胞中表达。鼻CpG位点在预测AsRh方面表现良好。

结论

我们在鼻刷中发现了哮喘和鼻炎的可复制DNA甲基化谱。与哮喘和鼻炎相关的宠物接触可能会影响鼻上皮甲基化。