Pharmacogenomics and Placebo Response in a Randomized Clinical Trial in Asthma
Year: 2019
Type: article
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.
DOI: 10.1002/cpt.1646
Institutions: Brigham and Women's Hospital, Harvard University
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: The HMS Laboratory of Systems Pharmacology, Weight loss-induced modification of the genomic network underlying obese asthma, Boston Biomedical Innovation Center, Center for Integrated Approached to Undiagnosed Diseases, Epidemiological, pharmacogenomic and clinical impact of catechol-O-methyltransferase on cardiovascular disease, G7971770453, G9000004051
OpenAlex ID: W2975264981