哮喘联盟

   摘要
   研究人员发现成千上万的基因位点参与复杂的性状和药物反应。然而，大多数情况下他们只能解释一小部分的遗传性状。确定“遗传缺失”的研究策略有多种，本研究通过在拉丁美洲哮喘患者中关于白三烯对沙丁胺醇的支气管扩张反应的作用结果来阐述复杂的基因-环境相互作用。使用白三烯调节药物治疗的患者，沙丁胺醇支气管舒张反应增加的表现更为明显。另外，导致白三烯产生的基因间的相互作用也可减少哮喘发生风险。由于遗传和药物的共同影响，携带某些等位基因组合的白三烯调节剂使用者，在使用支气管扩张剂后肺功能改善更好。基因和药物不同规则的相互作用(从个体效应到基因-基因-药物-药物的相互作用)和人群特殊效应都必须加以考虑。这些结果可以外推到其他复杂的表型。

 

（刘国梁 审校）
Pharmacogenomics. 2013 Jun;14(8):923-9. doi: 10.2217/pgs.13.70.

 

Role of interactions in pharmacogenetic studies: leukotrienes in asthma.
 

Via M, Tcheurekdjian H, González Burchard E.
 

Abstract
Researchers have identified thousands of loci involved in complex traits and drug response. However, in most cases they only explain a small proportion of the heritability of the trait. Among different strategies conducted to identify this 'missing heritability', here we illustrate the importance of complex gene-environment interactions using findings regarding the role of leukotrienes on the bronchodilator response to albuterol in Latino asthmatics. Patients managing their asthma with leukotriene-modifying medication presented higher increases in the bronchodilator response to albuterol. Moreover, interactions between genes responsible for leukotriene production were associated with a decreased risk of asthma. Combining genetic and pharmacologic effects, leukotriene-modifying users carrying certain combinations of alleles presented higher improvements in lung function after bronchodilator administration. Genes and drugs act at different orders of interaction (from individual effects to gene-gene-drug-drug interactions) and population-specific effects have to be considered. These results may be extrapolated to other complex phenotypes.

 

Pharmacogenomics. 2013 Jun;14(8):923-9. doi: 10.2217/pgs.13.70.