Wang Alberta L, Tantisira Kelan G
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States.
Expert Rev Precis Med Drug Dev. 2016;1(6):487-495. doi: 10.1080/23808993.2016.1269600. Epub 2016 Dec 20.
The genetics of severe asthma and asthma exacerbations are distinct from milder forms of asthma. Gene-environmental interactions contribute to the complexity and heterogeneity of severe asthma and asthma exacerbations, and pharmacogenomic studies have also identified genes that affect susceptibility to asthma exacerbations.
Studies on the genetics, gene-environment interactions, and pharmacogenomics of asthma exacerbations are reviewed. Multiple individual genetic variants have been identified to be associated with asthma exacerbations but each genetic polymorphism explains only a fraction of the disease and by itself is not able to translate into clinical practice. Research is shifting from candidate gene studies and genome wide association studies towards more integrative approaches to translate genetic findings into clinical diagnostic and therapeutic tools.
Integrative approaches combining polygenic or genomic data with multi-omics technologies have the potential to discover new biologic mechanisms and biomarkers for severe asthma and asthma exacerbations. Greater understanding of genomics and underlying biologic pathways will also lead to improved prevention and treatment, lowering costs, morbidity, and mortality. The utilization of genomic testing and personalized medicine may revolutionize asthma management, in particular for patients with severe, refractory asthma.
重度哮喘和哮喘急性发作的遗传学特征与轻度哮喘不同。基因与环境的相互作用导致了重度哮喘和哮喘急性发作的复杂性和异质性，药物基因组学研究也已确定了影响哮喘急性发作易感性的基因。
对哮喘急性发作的遗传学、基因与环境相互作用以及药物基因组学的研究进行了综述。已确定多个个体遗传变异与哮喘急性发作相关，但每个基因多态性仅能解释部分疾病，其本身无法转化为临床实践。研究正从候选基因研究和全基因组关联研究转向更综合的方法，以将遗传研究结果转化为临床诊断和治疗工具。
将多基因或基因组数据与多组学技术相结合的综合方法，有潜力发现重度哮喘和哮喘急性发作的新生物学机制和生物标志物。对基因组学和潜在生物学途径的更深入理解也将改善预防和治疗，降低成本、发病率和死亡率。基因组检测和个性化医疗的应用可能会彻底改变哮喘管理，尤其是对于重度难治性哮喘患者。
