No evidence of large genetic effects on steroid response in asthma patients - 19/04/17
, Kay Murphy, PhD a, Judong Shen, PhD b, ‡, Kijoung Song, PhD c, Matthew Nelson, PhD c, Soumitra Ghosh, PhD, MD cAbstract |
Background |
Inhaled corticosteroids (ICSs) are considered the most effective anti-inflammatory therapy for asthma control and management; however, there is substantial treatment response variability.
Objective |
We sought to identify genetic markers of ICS response by conducting the largest pharmacogenetic investigation to date in 2672 ICS-treated patients with asthma.
Methods |
Genotyping and imputation was performed in fluticasone furoate (FF) or fluticasone propionate–treated patients with asthma from 3 phase IIB and 4 phase IIIA randomized, double-blind, placebo-controlled, parallel group, multicenter studies. The primary end point analyzed was change in trough FEV1 (ΔFEV1) from baseline to 8 to 12 weeks of treatment.
Results |
More than 9.8 million common genetic variants (minor allele frequency ≥ 1%) were analyzed to test for association with ΔFEV1. No genetic variant met the prespecified threshold for statistical significance.
Conclusions |
This study provides no evidence to confirm previously reported associations between candidate genetic variants and ICS response (ΔFEV1) in patients with asthma. In addition, no variant satisfied the criterion for genome-wide significance in our study. Common genetic variants are therefore unlikely to prove useful as predictive biomarkers of ICS response in patients with asthma.
Le texte complet de cet article est disponible en PDF.Key words : Steroid response, asthma, fluticasone, genome-wide association studies, inhaled corticosteroids, pharmacogenetics
Abbreviations used : 1000G, FF, FP, GWAS, ICS, MAF, OEE, PC, SE
Plan
| This study was funded by GSK (study no. 116935). |
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| Disclosure of potential conflicts of interest: All authors were employees of GSK at the time of writing the article and held or currently hold stock in GSK. The 7 clinical studies referred to in this article and the subsequent pharmacogenetic evaluations were all funded by GSK. GSK was responsible for generating and interpreting the data, writing the article, and submitting it for publication. |
Vol 139 - N° 3
P. 797 - mars 2017 Retour au numéro
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