Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
Curr Opin Allergy Clin Immunol. 2013 Aug;13(4):399-409. doi: 10.1097/ACI.0b013e3283630c19.
Asthma is a chronic, complex disease that is treated with a combination of different therapies. However, interindividual variability in clinical responses to different therapies complicates asthma management. A personalized approach to asthma management could identify appropriate responders to specific agents or those that might be at an increased risk for adverse responses.
Pharmacogenetic studies of genes from the leukotriene, glucocorticoid, and beta2-adrenergic receptor pathways have improved our understanding of how gene variation determines therapeutic responses to different classes of antiasthma therapies. Such studies have previously been limited to retrospective analyses of candidate genes in the leukotriene, glucocorticoid, and beta2-adrenergic receptor pathways in trial cohorts. However, prospective genotype-stratified trials in asthma have recently been done and recent genome-wide association studies have identified novel pharmacogenetic loci.
It will be important to replicate previous genotypic associations in large clinical trial cohorts as future pharmacogenetic studies continue to focus on genome-wide approaches and the study of novel therapeutic pathways. This review of the pharmacogenetics of asthma highlights the contributions of genomics research to the future of personalized medicine in asthma and draws attention to the role of genetic biomarkers in predicting clinical responses to specific therapies.
哮喘是一种慢性、复杂的疾病，需要采用多种疗法联合治疗。然而，不同疗法对个体临床反应的差异使得哮喘管理变得复杂。采用个体化的哮喘管理方法可以识别对特定药物有反应的患者，或者那些可能对不良反应风险增加的患者。
白三烯、糖皮质激素和β2-肾上腺素能受体途径的基因的药物遗传学研究提高了我们对基因变异如何决定不同类别的抗哮喘治疗反应的理解。这些研究以前仅限于在试验队列中对候选基因进行回顾性分析。然而，最近在哮喘中进行了前瞻性的基于基因型的试验，全基因组关联研究也鉴定了新的药物遗传学位点。
随着未来的药物遗传学研究继续关注全基因组方法和新的治疗途径，在大型临床试验队列中复制以前的基因型关联将非常重要。本综述强调了基因组学研究对哮喘个体化医学未来的贡献，并提请注意遗传生物标志物在预测对特定治疗方法的临床反应中的作用。
