Morales Eva, Duffy David
Biomedical Research Institute of Murcia (IMIB-Arrixaca), University of Murcia, Murcia, Spain.
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
Front Pediatr. 2019 Dec 11;7:499. doi: 10.3389/fped.2019.00499. eCollection 2019.
Asthma is a heterogeneous disease that results from the complex interaction between genetic factors and environmental exposures that occur at critical periods throughout life. It seems plausible to regard childhood-onset and adult-onset asthma as different entities, each with a different pathophysiology, trajectory, and outcome. This review provides an overview about the role of genetics and gene-environment interactions in these two conditions. Looking at the genetic overlap between childhood and adult onset disease gives one window into whether there is a correlation, as well as to mechanism. A second window is offered by the genetics of the relationship between each type of asthma and other phenotypes e.g., obesity, chronic obstructive pulmonary disease (COPD), atopy, vitamin D levels, and inflammatory and immune status; and third, the genetic-specific responses to the many environmental exposures that influence risk throughout life, and particularly those that occur during early-life development. These represent a large number of possible combinations of genetic and environmental factors, at least 150 known genetic loci . tobacco smoke, outdoor air pollutants, indoor exposures, farming environment, and microbial exposures. Considering time of asthma onset extends the two-dimensional problem of gene-environment interactions to a three-dimensional problem, since identified gene-environment interactions seldom replicate for childhood and adult asthma, which suggests that asthma susceptibility to environmental exposures may biologically differ from early life to adulthood as a result of different pathways and mechanisms of the disease.
哮喘是一种异质性疾病，由遗传因素与一生中关键时期发生的环境暴露之间的复杂相互作用所致。将儿童期发病和成人期发病的哮喘视为不同的实体似乎是合理的，它们各自具有不同的病理生理学、病程和结局。本综述概述了遗传因素和基因 - 环境相互作用在这两种情况下的作用。研究儿童期和成人期发病疾病之间的遗传重叠，为是否存在相关性以及机制提供了一个窗口。另一个窗口是每种类型哮喘与其他表型（如肥胖、慢性阻塞性肺疾病（COPD）、特应性、维生素D水平以及炎症和免疫状态）之间关系的遗传学；第三，对一生中影响风险的许多环境暴露，特别是在生命早期发育过程中发生的环境暴露的基因特异性反应。这些代表了大量遗传和环境因素的可能组合，至少有150个已知的遗传位点，包括烟草烟雾、室外空气污染物、室内暴露、农业环境和微生物暴露。考虑哮喘发病时间将基因 - 环境相互作用的二维问题扩展为三维问题，因为已确定的基因 - 环境相互作用很少能在儿童期和成人期哮喘中重复出现，这表明由于疾病的不同途径和机制，哮喘对环境暴露的易感性在生命早期到成年期可能在生物学上有所不同。
