Keskin Ozlem, Farzan Niloufar, Birben Esra, Akel Hayriye, Karaaslan Cagatay, Maitland-van der Zee Anke H, Wechsler Michael E, Vijverberg Susanne J, Kalayci Omer
1Paediatric Allergy and Immunology Department, School of Medicine, Gaziantep University, Gaziantep, Turkey.
2Department of Respiratory Medicine, University of Amsterdam, Amsterdam UMC, Meibergdreef 9, Amsterdam, Netherlands.
Clin Transl Allergy. 2019 Jan 9;9:2. doi: 10.1186/s13601-018-0239-2. eCollection 2019.
There is wide variability in the response to inhaled corticosteroids (ICS) in asthma. While some of this heterogeneity of response is due to adherence and environmental causes, genetic variation also influences response to treatment and genetic markers may help guide treatment. Over the past years, researchers have investigated the relationship between a large number of genetic variations and response to ICS by performing pharmacogenomic studies. In this systematic review we will provide a summary of recent pharmacogenomic studies on ICS and discuss the latest insight into the potential functional role of identified genetic variants. To date, seven genome wide association studies (GWAS) examining ICS response have been published. There is little overlap between identified variants and methodologies vary largely. However, in vitro and/or in silico analyses provide additional evidence that genes discovered in these GWAS (e.g. , , , , ) might play a direct or indirect role in asthma/treatment response pathways. Furthermore, more than 30 candidate-gene studies have been performed, mainly attempting to replicate variants discovered in GWAS or candidate genes likely involved in the corticosteroid drug pathway. Single nucleotide polymorphisms located in , and the locus were positively replicated in independent populations. Although none of the genetic markers has currently reached clinical practise, these studies might provide novel insights in the complex pathways underlying corticosteroids response in asthmatic patients.
哮喘患者对吸入性糖皮质激素（ICS）的反应存在很大差异。虽然这种反应的异质性部分归因于依从性和环境因素，但基因变异也会影响治疗反应，基因标记可能有助于指导治疗。在过去几年中，研究人员通过开展药物基因组学研究，调查了大量基因变异与ICS反应之间的关系。在本系统评价中，我们将总结近期关于ICS的药物基因组学研究，并讨论已识别基因变异潜在功能作用的最新见解。迄今为止，已发表了7项考察ICS反应的全基因组关联研究（GWAS）。所识别的变异之间几乎没有重叠，且方法差异很大。然而，体外和/或计算机分析提供了额外证据，表明这些GWAS中发现的基因（如……）可能在哮喘/治疗反应途径中发挥直接或间接作用。此外，已经开展了30多项候选基因研究，主要试图重复GWAS中发现的变异或可能参与糖皮质激素药物途径的候选基因。位于……和……基因座的单核苷酸多态性在独立人群中得到了正向重复验证。虽然目前尚无基因标记应用于临床实践，但这些研究可能为哮喘患者糖皮质激素反应的复杂途径提供新的见解。
