DeVries Avery, Vercelli Donata
aGraduate Program in Cellular and Molecular Medicine bFunctional Genomics Laboratory, Arizona Respiratory Center cArizona Center for the Biology of Complex Diseases dDepartment of Cellular and Molecular Medicine eThe Bio5 Institute, University of Arizona, Tucson, Arizona, USA.
Curr Opin Allergy Clin Immunol. 2015 Oct;15(5):435-9. doi: 10.1097/ACI.0000000000000201.
Asthma and allergic diseases are among the most prevalent chronic noncommunicable diseases of childhood. Although epidemiologic studies suggest that asthma begins in the preschool years, the lack of firm diagnostic criteria to distinguish children who will wheeze only transiently during early-life lower respiratory illnesses from children who will wheeze persistently and develop asthma prevents pinpointing the time at which disease truly begins. Epigenetic mechanisms link gene regulation to environmental cues and developmental trajectories. This article reviews, the search for epigenetic predictors of asthma and/or allergy that can be identified already at birth and/or in early life.
DNA methylation signatures associated with asthma and/or allergy at birth, and time-dependent DNA methylation signatures associated with allergic disease phenotypes in early life have been identified.
The identification of early epigenetic predictors of allergic diseases points to a potential role of epigenetic mechanisms in regulating the inception of and the susceptibility to these diseases. Predictive signatures to more accurately estimate a child's risk for asthma and allergy may improve childhood asthma diagnosis. Moreover, understanding the biological implications of these signatures may help elucidate novel disease pathways and endotypes.
哮喘和过敏性疾病是儿童中最常见的慢性非传染性疾病。尽管流行病学研究表明哮喘始于学龄前,但缺乏明确的诊断标准来区分那些在生命早期下呼吸道疾病中仅短暂喘息的儿童和那些将持续喘息并发展为哮喘的儿童,这使得难以确定疾病真正开始的时间。表观遗传机制将基因调控与环境线索和发育轨迹联系起来。本文综述了寻找在出生时和/或生命早期即可识别的哮喘和/或过敏的表观遗传预测指标。
已确定与出生时哮喘和/或过敏相关的DNA甲基化特征,以及与生命早期过敏性疾病表型相关的时间依赖性DNA甲基化特征。
过敏性疾病早期表观遗传预测指标的识别表明表观遗传机制在调节这些疾病的起始和易感性方面具有潜在作用。更准确估计儿童哮喘和过敏风险的预测特征可能会改善儿童哮喘的诊断。此外,了解这些特征的生物学意义可能有助于阐明新的疾病途径和内型。