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Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers: a systematic review
Author(s) -
Farzan N.,
Vijverberg S. J. H.,
Arets H. G.,
Raaijmakers J. A. M.,
Maitlandvan der Zee A. H.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12844
Subject(s) - pharmacogenomics , inhaled corticosteroids , medicine , asthma , leukotriene , leukotriene c4 , systematic review , pharmacology , intensive care medicine , medline , dermatology , chemistry , biochemistry
Summary 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 ( LTM s) 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 LTM s were included if ≥1 of the following outcomes were studied: lung function, exacerbation rates or asthma symptoms. The studies of Single Nucleotide Polymorphisms ( SNP s) 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 LTM s (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 SNP s assessed in candidate gene studies were identified in a GWAS . No consistent reports were found for candidate gene studies of LTM s. In candidate gene studies of ICS , the most consistent results were found for rs28364072 in FCER 2. 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 FCER 2 gene [encoding for a low‐affinity IgE receptor ( CD 23)] and poor ICS response. Larger studies with well‐phenotyped patients are needed to assess the clinical applicability of ICS and LTM pharmacogenomics/genetics.