Davidson Elizabeth J, Yang Ivana V
Department of Medicine, University of Colorado School of Medicine.
Department of Epidemiology, Colorado School of Public Health, Aurora.
Curr Opin Allergy Clin Immunol. 2018 Apr;18(2):132-138. doi: 10.1097/ACI.0000000000000429.
Epigenetic marks are emerging as mediators of genetics and the environment on complex disease phenotypes, including childhood asthma and allergy.
Epigenome-wide association studies over the past year have added to the growing body of evidence supporting significant associations of epigenetic regulation of gene expression and asthma and allergy. Studies in children have identified signatures of eosinophils in peripheral blood, Th2 cell transcription factors and cytokines in peripheral blood mononuclear cells, and epithelial dysfunction in the respiratory epithelium. Importantly, studies at birth have begun to decipher the contribution of epigenetic marks to asthma inception. Few studies have also begun to address the contribution of genetics and the environment to these associations.
Next generation of epigenome-wide association studies that will deal with confounders, study the influence of the genetics and environment, and incorporate multiple datasets to provide better interpretation of the findings are on the horizon. Identification of key epigenetic marks that are shaped by genetics and the environment, and impact transcription of specific genes will help us have a better understanding of etiology, heterogeneity and severity of asthma, and will also empower us to develop biologically driven therapeutics and biomarkers for secondary prevention of this disease.
表观遗传标记正逐渐成为遗传学与环境因素作用于包括儿童哮喘和过敏在内的复杂疾病表型的介质。
过去一年的全表观基因组关联研究进一步补充了越来越多的证据，支持基因表达的表观遗传调控与哮喘和过敏之间存在显著关联。针对儿童的研究已确定外周血嗜酸性粒细胞、外周血单个核细胞中的Th2细胞转录因子和细胞因子的特征，以及呼吸道上皮的上皮功能障碍。重要的是，出生时的研究已开始解读表观遗传标记对哮喘发病的作用。也有少数研究开始探讨遗传因素和环境因素对这些关联的影响。
新一代全表观基因组关联研究即将开展，这些研究将处理混杂因素、研究遗传因素和环境因素的影响，并整合多个数据集以更好地解释研究结果。确定由遗传因素和环境因素塑造且影响特定基因转录的关键表观遗传标记，将有助于我们更好地理解哮喘的病因、异质性和严重程度，还将使我们有能力开发基于生物学的治疗方法和生物标志物用于该疾病的二级预防。
