title: Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation.
abstract: Genetic associations of the response to inhaled corticosteroids (ICSs) during an asthma exacerbation are unknown.
  
  
  
  To evaluate the role of genetic variants in the therapeutic response to high-dose ICS in children with moderate-to-severe asthma exacerbations.
  
  
  
  Eighty-two children (56 boys/26 girls, mean age 9.6 ± 3.2 years) with moderate-severe asthma exacerbation were genotyped for eight single-nucleotide polymorphisms that were a priori associated with ICS response in chronic asthma treatment: glucocorticosteroid receptor (NR3C1) rs41423247; corticotrophin-releasing hormone receptor1 (CRHR1) rs242939, rs242941, and rs1876828; T-box 21 (TBX21) rs2240017; glucocorticoid-induced transcript 1 (GLCCl1); and T gene rs3099266 and rs2305089. Children were treated with a single high-dose (4000 μg) fluticasone propionate given by a nebulizer followed by 1000 μg/day of inhaled fluticasone propionate for 6 days. Primary outcome measure was the improvement in FEV1 at 4 h.
  
  
  
  Mean FEV1 was 71.7 ± 14.2% at presentation. Overall, fluticasone treatment resulted in a significant improvement in asthma score and FEV1 (p < 0.0001 for both). Children with the GG genotype at NR3C1 rs41423247 (n = 26) had a higher improvement in FEV1 [24.2% (interquartile range 11.5-36.3)] compared to those with CG+CC (n = 19), [7.9% (interquartile range 6.1-24.6) (p = 0.006)].
  
  
  
  Homozygosity for the G allele at rs41423247 of the glucocorticosteroid receptor (NR3C1) gene is associated with a higher improvement in FEV1 at 4 h in children with moderate-to-severe asthma exacerbation treated with high-dose ICS. This observation may have important clinical implications especially for children who use systemic steroids frequently for recurrent asthma exacerbations.
authors.affiliation: Pediatric Allergy and Immunology Department, Gaziantep University School of Medicine, Gaziantep, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Keskin
authors.affiliation: Department of Pediatrics, Gaziantep University School of Medicine, Gaziantep, Turkey.
authors.forename: Ünal
authors.initials: Ü
authors.lastname: Uluca
authors.affiliation: Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: Esra
authors.initials: E
authors.lastname: Birben
authors.affiliation: Department of Pediatrics, Gaziantep University School of Medicine, Gaziantep, Turkey.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Coşkun
authors.affiliation: Pediatric Allergy and Immunology Department, Gaziantep University School of Medicine, Gaziantep, Turkey.
authors.forename: Mehmet Yasar
authors.initials: MY
authors.lastname: Ozkars
authors.affiliation: Department of Pediatrics, Gaziantep University School of Medicine, Gaziantep, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Keskin
authors.affiliation: Pediatric Allergy and Immunology Department, Gaziantep University School of Medicine, Gaziantep, Turkey.
authors.forename: Ercan
authors.initials: E
authors.lastname: Kucukosmanoglu
authors.affiliation: Pediatric Allergy and Asthma Unit, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: Omer
authors.initials: O
authors.lastname: Kalayci
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D054316:Biomarkers, Pharmacological / Q000378:metabolism*; D002648:Child; D005260:Female; D000068298:Fluticasone / Q000627:therapeutic use*; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D054316:Biomarkers, Pharmacological; C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D000068298:Fluticasone
keywords: asthma; child; exacerbation; gene; inhaled corticosteroid; pharmacogenetics