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Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation
Author(s) -
Keskin Ozlem,
Uluca Ünal,
Birben Esra,
Coşkun Yavuz,
Ozkars Mehmet Yasar,
Keskin Mehmet,
Kucukosmanoglu Ercan,
Kalayci Omer
Publication year - 2016
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12566
Subject(s) - medicine , fluticasone propionate , interquartile range , asthma , fluticasone , exacerbation
Background Genetic associations of the response to inhaled corticosteroids ( ICS s) during an asthma exacerbation are unknown. Objective To evaluate the role of genetic variants in the therapeutic response to high‐dose ICS in children with moderate‐to‐severe asthma exacerbations. Methods 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 ( NR 3C1) rs41423247; corticotrophin‐releasing hormone receptor1 ( CRHR 1) rs242939, rs242941, and rs1876828; T‐box 21 ( TBX 21) rs2240017; glucocorticoid‐induced transcript 1 ( GLCC l1) ; 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 FEV 1 at 4 h. Results Mean FEV 1 was 71.7 ± 14.2% at presentation. Overall, fluticasone treatment resulted in a significant improvement in asthma score and FEV 1 (p < 0.0001 for both). Children with the GG genotype at NR 3C1 rs41423247 (n = 26) had a higher improvement in FEV 1 [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)]. Conclusion Homozygosity for the G allele at rs41423247 of the glucocorticosteroid receptor ( NR 3C1 ) gene is associated with a higher improvement in FEV 1 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.