Open AccessGenetic associations of the response to inhaled corticosteroids in asthma: a systematic review
Author(s) -
Keskin Ozlem,
Farzan Niloufar,
Birben Esra,
Akel Hayriye,
Karaaslan Cagatay,
Maitlandvan der Zee Anke H.,
Wechsler Michael E.,
Vijverberg Susanne J.,
Kalayci Omer
Publication year - 2019
Publication title -
clinical and translational allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.979
H-Index - 37
ISSN - 2045-7022
DOI - 10.1186/s13601-018-0239-2
Subject(s) - pharmacogenomics , genome wide association study , genetic association , candidate gene , single nucleotide polymorphism , medicine , pharmacogenetics , asthma , drug response , genetic variation , computational biology , bioinformatics , genetic architecture , genetics , gene , biology , quantitative trait locus , immunology , drug , genotype , pharmacology
Abstract 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. 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 in GLCCI1 , NR3C1 and the 17q21 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.