Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers: a systematic review

Farzan, Niloufar; Vijverberg, Susanne J. H.; Arets, H.G.M.; Raaijmakers, J. A. M.; Zee, Anke‐Hilse Maitland‐van der

doi:10.1111/cea.12844

Cited by 38 publications

(43 citation statements)

References 93 publications

(279 reference statements)

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“…A recent systematic review by Farzan et al [41] showed that genetic variants of three genes (GLCCI1, CRHR1, and FCER2) have been successfully replicated in at least one independent study.…”

Section: Ics Responsementioning

confidence: 99%

“…Initially, candidate-gene studies on LTRA response focused on genes within pharmacological leukotriene pathway, such as leukotriene A4 hydrolase (LTC4s), 5-lipoxygenase (ALOX5), leukotriene A4 hydrolase (LTA4H), and cysteinyl leukotriene receptor 1 (CysLTR1) [41]. In addition, genes influencing LTM pharmacokinetics such as CYP enzymes (CYP3A4, CYP2C9) and transporter genes (SLCO2B1, MRP1/ ABCC1) have also been investigated [53,54].…”

Section: Leukotriene Modifiers Responsementioning

confidence: 99%

“…In addition, genes influencing LTM pharmacokinetics such as CYP enzymes (CYP3A4, CYP2C9) and transporter genes (SLCO2B1, MRP1/ ABCC1) have also been investigated [53,54]. A recent systematic review showed that despite a large amount of pharmacogenetics LTRA studies; only variants in two genes, ALOX5 and MRP1, have been replicated to show similar outcomes of LTRA response at least once [41]. Two genetic variants of ALOX5 have been associated with altered LTRA response; tandem repeat of the Sp1-binding domain and a SNP at position rs2115819.…”

Section: Leukotriene Modifiers Responsementioning

confidence: 99%

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Treatment response heterogeneity in asthma: the role of genetic variation

Vijverberg

Farzan

Slob

et al. 2017

Expert Review of Respiratory Medicine

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Introduction: Asthmatic patients show a large heterogeneity in response to asthma medication. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with treatment outcomes. Areas covered: This review focuses on the current knowledge of genetic variants influencing treatment response to the most commonly used asthma medicines: short-and long-acting beta-2 agonists (SABA/ LABA), inhaled corticosteroids (ICS) and leukotriene modifiers. This review shows that various genetic variants have been identified, but none are currently used to guide asthma treatment. One of the most promising genetic variants is the Arg16 variant in the ADRB2 gene to guide LABA treatment in asthmatic children. Expert commentary: Poor replication of initially promising results and the low fraction of variability accounted for by single genetic variants inhibit pharmacogenetic findings to reach the asthma clinic. Nevertheless, the identification of genetic variation influencing treatment response does provide more insights in the complex processes underlying response and might identify novel targets for treatment. There is a need to report measures of clinical validity, to perform precision-medicine guided trials, as well as to understand how genetic variation interacts with environmental factors. In addition, systems biology approaches might be able to show a more complete picture of these complex interactions.ARTICLE HISTORY

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“…A recent systematic review by Farzan et al [41] showed that genetic variants of three genes (GLCCI1, CRHR1, and FCER2) have been successfully replicated in at least one independent study.…”

Section: Ics Responsementioning

confidence: 99%

Section: Leukotriene Modifiers Responsementioning

confidence: 99%

Section: Leukotriene Modifiers Responsementioning

confidence: 99%

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Treatment response heterogeneity in asthma: the role of genetic variation

Vijverberg

Farzan

Slob

et al. 2017

Expert Review of Respiratory Medicine

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“…According to the GINA guidelines, inhaled corticosteroids (ICS) combined with short‐acting β2 agonists (SABA), or long‐acting β2 agonists (LABA) are the preferred treatment for persistent asthma symptoms . However, even in asthmatic children with a good adherence to maintenance treatment and an adequate inhalation technique, there is a high variability in response to treatment; approximately ten percent of the patients still have serious complaints despite high doses of ICS …”

Section: Introductionmentioning

confidence: 99%

“…Pharmaco genomics is a subfield of genomics which assesses the effect of DNA variants on the patient's response to medication . Modulating effects of genetic variations, both focusing on asthma onset (genomics) as well as response to therapeutic agents (pharmacogenomics), have been reported in numerous studies . Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation in the human genome and are commonly investigated in pharmacogenomics studies using candidate gene and genome wide association studies (GWAS).…”

Section: Introductionmentioning

confidence: 99%

The use of pharmacogenomics, epigenomics, and transcriptomics to improve childhood asthma management: Where do we stand?

Farzan

Vijverberg

Kabesch

et al. 2018

Pediatric Pulmonology

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Asthma is a complex multifactorial disease and it is the most common chronic disease in children. There is a high variability in response to asthma treatment, even in patients with good adherence to maintenance treatment, and a correct inhalation technique. Distinct underlying disease mechanisms in childhood asthma might be the reason of this heterogeneity. A deeper knowledge of the underlying molecular mechanisms of asthma has led to the recent development of advanced and mechanism-based treatments such as biologicals. However, biologicals are recommended only for patients with specific asthma phenotypes who remain uncontrolled despite high dosages of conventional asthma treatment. One of the main unmet needs in their application is lack of clinically available biomarkers to individualize pediatric asthma management and guide treatment. Pharmacogenomics, epigenomics, and transcriptomics are three omics fields that are rapidly advancing and can provide tools to identify novel asthma mechanisms and biomarkers to guide treatment. Pharmacogenomics focuses on variants in the DNA, epigenomics studies heritable changes that do not involve changes in the DNA sequence but lead to alteration of gene expression, and transcriptomics investigates gene expression by studying the complete set of mRNA transcripts in a cell or a population of cells. Advances in high-throughput technologies and statistical tools together with well-phenotyped patient inclusion and collaborations between different centers will expand our knowledge of underlying molecular mechanisms involved in disease onset and progress. Furthermore, it could help to select and stratify appropriate therapeutic strategies for subgroups of patients and hopefully bring precision medicine to daily practice.

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