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Pharmacogenomics and Placebo Response in a Randomized Clinical Trial in Asthma
- Source :
- Clin Pharmacol Ther
- Publication Year :
- 2019
-
Abstract
- Genetic variation may differentially modify drug and placebo treatment effects in randomized clinical trials. In asthma, although lung function and asthma control improvements are commonplace with placebo, pharmacogenomics of placebo vs. drug response remains unexamined. In a genomewide association study of subjective and objective outcomes with placebo treatment in Childhood Asthma Management Program of nedocromil/budesonide vs. placebo (N = 604), effect estimates for lead single nucleotide polymorphisms (SNPs) were compared across arms. The coughing/wheezing lead SNP, rs2392165 (β = 0.94; P = 1.10E-07) mapped to BBS9, a gene implicated in lung development that contains a lung function expression quantitative trait locus. The effect was attenuated with budesonide (Pinteraction = 1.48E-07), but not nedocromil (Pinteraction = 0.06). The lead forced vital capacity SNP, rs12930749 (β = -5.80; P = 1.47E-06), mapped to KIAA0556, a locus genomewide associated with respiratory diseases. The rs12930749 effect was attenuated with budesonide (Pinteraction = 1.32E-02) and nedocromil (Pinteraction = 1.09E-02). Pharmacogenomic analysis revealed differential effects with placebo and drug treatment that could potentially guide precision drug development in asthma.
- Subjects :
- Budesonide
Nedocromil
Male
medicine.medical_specialty
Vital capacity
Vital Capacity
Single-nucleotide polymorphism
Placebo
030226 pharmacology & pharmacy
Polymorphism, Single Nucleotide
Article
law.invention
03 medical and health sciences
0302 clinical medicine
Randomized controlled trial
law
Internal medicine
medicine
Humans
Pharmacology (medical)
Anti-Asthmatic Agents
Patient Reported Outcome Measures
Child
Asthma
Respiratory Sounds
Pharmacology
business.industry
medicine.disease
Placebo Effect
respiratory tract diseases
Pharmacogenomic Testing
Cytoskeletal Proteins
Treatment Outcome
Cough
030220 oncology & carcinogenesis
Pharmacogenomics
Female
business
Microtubule-Associated Proteins
medicine.drug
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Clin Pharmacol Ther
- Accession number :
- edsair.doi.dedup.....6b961ad367964eb4d5268fd0d8e13867