title: No evidence of large genetic effects on steroid response in asthma patients.
abstract: 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.
authors: GSK, Stevenage, United Kingdom.
authors: Michael
authors: M
authors: Mosteller
authors: GSK, Stevenage, United Kingdom. Electronic address: louise.k.hosking@gsk.com.
authors: Louise
authors: L
authors: Hosking
authors: GSK, Stevenage, United Kingdom.
authors: Kay
authors: K
authors: Murphy
authors: GSK, Research Triangle Park, NC.
authors: Judong
authors: J
authors: Shen
authors: GSK, Upper Merion, Pa.
authors: Kijoung
authors: K
authors: Song
authors: GSK, Upper Merion, Pa.
authors: Matthew
authors: M
authors: Nelson
authors: GSK, Upper Merion, Pa.
authors: Soumitra
authors: S
authors: Ghosh
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000328:Adult; D000730:Androstadienes / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; C523187:fluticasone furoate
keywords: Steroid response; asthma; fluticasone; genome-wide association studies; inhaled corticosteroids; pharmacogenetics