The Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115; email:
Annu Rev Pharmacol Toxicol. 2015;55:129-47. doi: 10.1146/annurev-pharmtox-010814-124543. Epub 2014 Sep 29.
The response to drug treatment in asthma is a complex trait and is markedly variable even in patients with apparently similar clinical features. Pharmaco-genomics, which is the study of variations of human genome characteristics as related to drug response, can play a role in asthma therapy. Both a traditional candidate-gene approach to conducting genetic association studies and genome-wide association studies have provided an increasing list of genes and variants associated with the three major classes of asthma medications: β2-agonists, inhaled corticosteroids, and leukotriene modifiers. Moreover, a recent integrative, systems-level approach has offered a promising opportunity to identify important pharmacogenomics loci in asthma treatment. However, we are still a long way away from making this discipline directly relevant to patients. The combination of network modeling, functional validation, and integrative omics technologies will likely be needed to move asthma pharmacogenomics closer to clinical relevance.
哮喘的药物治疗反应是一种复杂的特征,即使在临床表现相似的患者中也存在明显的差异。药物基因组学是研究人类基因组特征与药物反应的关系,它可以在哮喘治疗中发挥作用。传统的候选基因方法和全基因组关联研究都提供了越来越多与哮喘三种主要药物类别相关的基因和变体:β2-激动剂、吸入皮质类固醇和白三烯调节剂。此外,最近一种综合的、系统水平的方法为确定哮喘治疗中重要的药物基因组学基因座提供了一个有前途的机会。然而,要使这一学科与患者直接相关,我们还有很长的路要走。将网络建模、功能验证和综合组学技术相结合,可能有助于将哮喘药物基因组学更接近临床相关性。