N Farzan1,2, S J H Vijverberg1,2, H G Arets3, J A M Raaijmakers1, A H Maitland-van der Zee1,2. 1. Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands. 2. Department of Respiratory Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands. 3. Department of Paediatric Pulmonology, University Medical Centre Utrecht, Utrecht, the Netherlands.
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). CONCLUSION AND CLINICAL RELEVANCE: 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.
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). CONCLUSION AND CLINICAL RELEVANCE: 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: Michael J McGeachie; George L Clemmer; Boris Hayete; Heming Xing; Karl Runge; Ann Chen Wu; Xiaofeng Jiang; Quan Lu; Bruce Church; Iya Khalil; Kelan Tantisira; Scott Weiss Journal: J Allergy Clin Immunol Date: 2018-03-02 Impact factor: 10.793
Authors: Natalia Hernandez-Pacheco; Susanne J Vijverberg; Esther Herrera-Luis; Jiang Li; Yang Yie Sio; Raquel Granell; Almudena Corrales; Cyrielle Maroteau; Ryan Lethem; Javier Perez-Garcia; Niloufar Farzan; Katja Repnik; Mario Gorenjak; Patricia Soares; Leila Karimi; Maximilian Schieck; Lina Pérez-Méndez; Vojko Berce; Roger Tavendale; Celeste Eng; Olaia Sardon; Inger Kull; Somnath Mukhopadhyay; Munir Pirmohamed; Katia M C Verhamme; Esteban G Burchard; Michael Kabesch; Daniel B Hawcutt; Erik Melén; Uroš Potočnik; Fook Tim Chew; Kelan G Tantisira; Steve Turner; Colin N Palmer; Carlos Flores; Maria Pino-Yanes; Anke H Maitland-van der Zee Journal: Eur Respir J Date: 2021-05-13 Impact factor: 16.671