title: FCER2 T2206C variant associated with chronic symptoms and exacerbations in steroid-treated asthmatic children.
abstract: BACKGROUND
  The T2206C FCER2 variant was found previously to be associated with IgE levels, exacerbation rates and decreased FCER2 expression in children on inhaled corticosteroids (ICS) participating in a clinical trial. This finding has not been replicated. We sought to replicate the association between the FCER2 gene and exacerbations in children with asthma. In addition, we tested the hypothesis that the T2206C variant may be associated with other markers of steroid resistance such as asthma symptom scores and asthma medication use.
  
  
  METHODS
  The influence of the T2206C variant on asthma exacerbations (emergency department visits or hospitalization), symptoms scores and medication use was explored using data from two populations of asthmatic children using ICS: Pharmacogenetics of Asthma medication in Children: Medication with ANti-inflammatory effects study (n = 386) and BREATHE study (n = 939).
  
  
  RESULTS
  The T2206C variant was associated with increased risk of asthma-related hospital visits in both cohorts (OR: 1.91, 95% CI: 1.08-3.40), and meta-analysis with previously published results was highly significant (OR: 2.38, 95% CI: 1.47-3.85, P = 0.0004). The FCER2 variant was also associated with increased risk of uncontrolled asthma measured by Asthma Control Questionnaire (OR: 2.64, 95% CI: 1.00-6.98) and was associated with increased daily steroid dose (OR: 2.46, 95% CI: 1.38-4.39).
  
  
  CONCLUSIONS
  The association between the FCER2 T2206C variant and asthma-related hospitalizations in steroid-treated asthma appears robust and may also be associated with other indicators of lack of ICS efficacy such as asthma symptoms and a requirement for higher daily doses of ICS. Our results suggest that the FCER2 T2206C variant might be a useful pharmacogenetic predictor of steroid refractory patients.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmacoepidemiology & Clinical Pharmacology, Faculty of Science, Utrecht University, Utrecht, the Netherlands.
authors.forename: E S
authors.initials: ES
authors.lastname: Koster
authors.forename: A-H
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.forename: R
authors.initials: R
authors.lastname: Tavendale
authors.forename: S
authors.initials: S
authors.lastname: Mukhopadhyay
authors.forename: S J H
authors.initials: SJ
authors.lastname: Vijverberg
authors.forename: J A M
authors.initials: JA
authors.lastname: Raaijmakers
authors.forename: C N A
authors.initials: CN
authors.lastname: Palmer
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017455:Receptors, IgE / Q000235:genetics*; D013256:Steroids / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; C546930:FCER2 protein, human; D037181:Lectins, C-Type; D017455:Receptors, IgE; D013256:Steroids