Institute of Environmental Medicine and Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
J Intern Med. 2012 Aug;272(2):108-20. doi: 10.1111/j.1365-2796.2012.02555.x.
There is good evidence that both inherited and environmental factors influence the risk of developing asthma. Only recently, large well-designed studies have been undertaken with the power to identify the genetic causes for asthma, and methods developed in parallel with the Human Genome Project, such as gene expression and epigenetic studies, have made large-scale analyses of functional genetics possible. In this review, we discuss the recent findings from genetic and genomic research studies of asthma, particularly severe asthma, and highlight specific genes for which there are multiple lines of evidence for involvement in asthma pathogenesis. Bio-ontologic enrichment analyses of the most recently identified asthma-related genes point to attributes such as 'molecular and signal transducer activity' and 'immune system processes', which indicates the importance of immunoregulation and inflammatory response in the pathogenesis of asthma. Finally, we discuss how genetic and environmental factors jointly influence asthma susceptibility and summarize how the results may increase understanding of the pathophysiology of asthma-related diseases.
有充分的证据表明，遗传和环境因素都会影响哮喘的发病风险。直到最近，才进行了大规模、精心设计的研究，以确定哮喘的遗传原因，并且与人类基因组计划并行开发的方法，如基因表达和表观遗传学研究，使得对功能遗传学进行大规模分析成为可能。在这篇综述中，我们讨论了哮喘，特别是严重哮喘的遗传和基因组研究的最新发现，并强调了一些特定基因，这些基因有多个证据表明它们与哮喘发病机制有关。最近发现的与哮喘相关的基因的生物本体论富集分析指出了“分子和信号转导活性”和“免疫系统过程”等属性，这表明免疫调节和炎症反应在哮喘发病机制中的重要性。最后，我们讨论了遗传和环境因素如何共同影响哮喘易感性，并总结了这些结果如何增加对哮喘相关疾病病理生理学的理解。
