title: Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers: a systematic review.
abstract: BACKGROUND
  Pharmacogenetics studies of anti-inflammatory medication of asthma have expanded rapidly in recent decades, but the clinical value of their findings remains limited.
  
  
  OBJECTIVE
  To perform a systematic review of pharmacogenomics and pharmacogenetics of inhaled corticosteroids (ICS) and leukotriene modifiers (LTMs) in patients with asthma.
  
  
  METHODS
  Articles published between 1999 and June 2015 were searched using PubMed and EMBASE. Pharmacogenomics/genetics studies of patients with asthma using ICS or LTMs were included if ≥1 of the following outcomes were studied: lung function, exacerbation rates or asthma symptoms. The studies of Single Nucleotide Polymorphisms (SNPs) that had been replicated at least once were assessed in more detail.
  
  
  RESULTS
  In total, 59 publications were included in the systematic review: 26 addressed LTMs (including two genomewide Genome-Wide association studies [GWAS]) and 33 addressed ICS (including four GWAS). None of the GWAS reported similar results. Furthermore, none of the SNPs assessed in candidate gene studies were identified in a GWAS. No consistent reports were found for candidate gene studies of LTMs. In candidate gene studies of ICS, the most consistent results were found for rs28364072 in FCER2. This SNP was associated with all three outcomes of poor response, and the largest effect was reported with the risk of exacerbations (hazard ratio, 3.95; 95% CI, 1.64-9.51).
  
  
  CONCLUSIONS
  There is a lack of replication of genetic variants associated with poor ICS or LTM response. The most consistent results were found for the FCER2 gene [encoding for a low-affinity IgE receptor (CD23)] and poor ICS response. Larger studies with well-phenotyped patients are needed to assess the clinical applicability of ICS and LTM pharmacogenomics/genetics.
authors: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.|Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors: N
authors: N
authors: Farzan
authors: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.|Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors: S J H
authors: SJ
authors: Vijverberg
authors: Department of Paediatric Pulmonology, University Medical Centre Utrecht, Utrecht, the Netherlands.
authors: H G
authors: HG
authors: Arets
authors: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
authors: J A M
authors: JA
authors: Raaijmakers
authors: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.|Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors: A H
authors: AH
authors: Maitland-van der Zee
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology*; D000483:Alleles; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D020024:Leukotriene Antagonists
keywords: asthma; inhaled corticosteroids; leukotriene modifiers; pharmacogenetics; pharmacogenomics