Role of epigenetics in the development of childhood asthma.
Role of epigenetics in the development of childhood asthma.
复制标题
DOI：
10.1097/aci.0000000000000429
复制
发表时间：
2018-04
影响因子：
2.8
通讯作者：
Yang IV
中科院分区：
文献类型：
--
作者：
Davidson EJ;Yang IV
表观遗传标记正在成为复杂疾病表型（包括儿童哮喘和过敏）的遗传和环境调节因素。过去一年的全表观基因组关联研究（EWAS）增加了越来越多的证据，支持基因表达的表观遗传调控与哮喘和过敏之间的显着关联。对儿童的研究已经确定了外周血中嗜酸性粒细胞、外周血单核细胞中 Th2 细胞转录因子和细胞因子以及呼吸道上皮中上皮功能障碍的特征。重要的是，出生时的研究已经开始破译表观遗传标记对哮喘发病的影响。很少有研究也开始探讨遗传和环境对这些关联的影响。下一代 EWAS 即将出现，它将处理混杂因素、研究遗传学和环境的影响，并整合多个数据集以更好地解释研究结果。识别由遗传学和环境形成的关键表观遗传标记以及影响特定基因的转录将有助于我们更好地了解哮喘的病因、异质性和严重程度，也将使我们能够开发生物驱动的治疗方法和生物标志物以用于该疾病的二级预防。
Epigenetic marks are emerging as mediators of genetics and the environment on complex disease phenotypes, including childhood asthma and allergy. Epigenome-wide association studies (EWAS) 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 EWAS 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.