No evidence of large genetic effects on steroid response in asthma patients

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 (Delta FEV1) 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 DFEV1. No genetic variant met the prespecified threshold for statistical significance. Conclusions: This study provides no evidence to confirmpreviously reported associations between candidate genetic variants and ICS response (Delta FEV1) 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.