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哮喘和过敏中的基因-环境相互作用:开端的结束?

Gene-environment interactions in asthma and allergy: the end of the beginning?

机构信息

Arizona Respiratory Center, Arizona Center for the Biology of Complex Diseases (ABCD), and Department of Cell Biology, College of Medicine, University of Arizona, Tucson, Arizona, USA.

出版信息

Curr Opin Allergy Clin Immunol. 2010 Apr;10(2):145-8. doi: 10.1097/ACI.0b013e32833653d7.

Abstract

PURPOSE OF REVIEW

The pathogenesis of asthma and allergy typically involves not only distinct genetic and environmental factors, but also interactions between the two. Innate-immunity genes [particularly CD14, toll-like receptor (TLR)4 and TLR2, the critical mediators of responses to bacteria in the extracellular space] play a prominent role in gene-environment interactions relevant to asthma-related phenotypes because the interaction between microbial load and the innate-immune system is a critical determinant of both immune function and allergy/asthma susceptibility. This review presents recent findings illustrating the role of gene-environment interactions in asthma/allergy susceptibility.

RECENT FINDINGS

Population studies have extended our understanding of the role of CD14 and innate-immune genes in the interplay between genetic variants and the environment, highlighting the complexity of these interactions and their significant influence on susceptibility to asthma and allergy.

SUMMARY

Gene-environment interactions have become a leitmotiv in asthma and allergy genetics, especially over the last 3 years. The next challenge awaiting asthma and allergy geneticists will be to define the extent to which the search for gene-environment interactions can be successfully integrated with hypothesis-generating, genome-wide approaches aimed at the identification of genetic variants involved in the pathogenesis of complex-lung diseases.

摘要

目的综述

哮喘和过敏的发病机制不仅涉及独特的遗传和环境因素,还涉及两者之间的相互作用。先天免疫基因(特别是 CD14、Toll 样受体(TLR)4 和 TLR2,它们是细胞外空间细菌反应的关键介质)在与哮喘相关表型相关的基因-环境相互作用中发挥着重要作用,因为微生物负荷与先天免疫系统之间的相互作用是决定免疫功能和过敏/哮喘易感性的关键决定因素。这篇综述介绍了最近的研究结果,这些结果说明了基因-环境相互作用在哮喘/过敏易感性中的作用。

最近的发现

人群研究扩展了我们对 CD14 和先天免疫基因在遗传变异与环境相互作用中的作用的理解,突出了这些相互作用的复杂性及其对哮喘和过敏易感性的显著影响。

总结

基因-环境相互作用已成为哮喘和过敏遗传学的主题,尤其是在过去 3 年中。哮喘和过敏遗传学家面临的下一个挑战将是确定在多大程度上可以成功地将寻找基因-环境相互作用与生成假说的、全基因组的方法相结合,这些方法旨在确定参与复杂肺部疾病发病机制的遗传变异。

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