Genetic associations of the response to inhaled corticosteroids in asthma: a systematic review

AbstractThere 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.GLCCI1,FBXL7,T gene,ALLC,CMTR1) 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 inGLCCI1,NR3C1 and the17q21 locus were positively replicated in independent populations. Although none of the genetic markers has currently reached clinical practise, these studies might provide novel insigh...
Source: Clinical and Translational Allergy - Category: Allergy & Immunology Source Type: research