March Michael E, Sleiman Patrick M A, Hakonarson Hakon
The Abramson Research Center of the Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Discov Med. 2011 Jan;11(56):35-45.
Asthma and allergic diseases are complex conditions caused by a combination of genetic and environmental factors. More than 100 genes have been associated with asthma and related conditions through candidate gene approaches, but issues of insufficient replication have made conclusions difficult to draw. Despite this, several overarching themes in the biology and pathogenesis of asthma have been revealed as a result of this work. In mid-2007, the first genome wide association study (GWAS) targeting asthma was published, and in the intervening years more than a dozen such studies have been reported examining asthma, allergic diseases, and related intermediate phenotypes and quantitative traits. A few previously suspected genetic variants have been confirmed in these studies as asthma susceptibility loci, or as loci contributing to disease severity or response to treatment. Additionally, unexpected and largely uncharacterized genes have been identified as new susceptibility loci for asthma, altering lung function or perturbing immune function. In this review, we summarize these GWAS, as well as the functional themes and characteristics underlying asthma that have been revealed through decades of genetic and genomic research.
哮喘和过敏性疾病是由遗传和环境因素共同作用引起的复杂病症。通过候选基因方法，已有100多个基因与哮喘及相关病症相关联，但复制不足的问题使得难以得出结论。尽管如此，这项工作还是揭示了哮喘生物学和发病机制中的几个总体主题。2007年年中，首个针对哮喘的全基因组关联研究（GWAS）发表，在随后的几年里，又有十几项此类研究报告，研究对象包括哮喘、过敏性疾病以及相关的中间表型和数量性状。在这些研究中，一些先前怀疑的基因变异已被确认为哮喘易感性位点，或作为影响疾病严重程度或治疗反应的位点。此外，一些意想不到且基本未被表征的基因已被鉴定为哮喘的新易感位点，它们会改变肺功能或扰乱免疫功能。在这篇综述中，我们总结了这些全基因组关联研究，以及通过数十年的遗传和基因组研究揭示的哮喘潜在功能主题和特征。
