Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation
Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation
复制标题
DOI：
10.1111/pai.12566
复制
发表时间：
2016-08-01
影响因子：
4.4
通讯作者：
Kalayci, Omer
中科院分区：
文献类型：
--
作者：
Keskin, Ozlem;Uluca, Unal;Kalayci, Omer
背景哮喘急性发作期间对吸入皮质类固醇（ICS）反应的遗传相关性尚不清楚。目的评估遗传变异在中重度哮喘急性发作儿童对高剂量ICS治疗反应中的作用。方法82名儿童（56名男孩/26名女孩，平均年龄9.6 ± 3.2岁）中重度哮喘急性发作的患者进行了基因分型，与慢性哮喘治疗中ICS反应先验相关的核苷酸多态性：糖皮质激素受体（NR 3C 1）rs 41423247;促肾上腺皮质激素释放激素受体1（CRHR 1）rs 242939、rs 242941和rs 1876828; T-box 21（TBX 21）rs 2240017;糖皮质激素诱导的转录物1（GLCC 11）;和T基因rs3099266和rs 2305089。儿童接受单次高剂量（4000 g）丙酸氟替卡松治疗，通过雾化器给药，随后1000 g/天吸入丙酸氟替卡松，持续6天。主要结果的措施是改善FEV 1在4小时。结果平均FEV 1为71.7 +/- 14.2%在介绍。总体而言，氟替卡松治疗导致哮喘评分和FEV 1显著改善（两者均为p < 0.0001）。NR 3C 1 rs 41423247 GG基因型的儿童（n = 26）FEV 1改善更高[24.2%（四分位距11.5-36.3）]与CG+CC组（n = 19）相比，[7.9%（四分位数间距6.1-24.6）结论糖皮质激素受体（NR 3C 1）rs 41423247位点G等位基因纯合性在接受大剂量ICS治疗的中重度哮喘急性发作儿童中，基因与4小时FEV 1的较高改善相关。这一观察结果可能具有重要的临床意义，特别是对于经常使用全身性类固醇治疗复发性哮喘急性发作的儿童。
BackgroundGenetic associations of the response to inhaled corticosteroids (ICSs) during an asthma exacerbation are unknown.ObjectiveTo evaluate the role of genetic variants in the therapeutic response to high-dose ICS in children with moderate-to-severe asthma exacerbations.MethodsEighty-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 g) fluticasone propionate given by a nebulizer followed by 1000 g/day of inhaled fluticasone propionate for 6 days. Primary outcome measure was the improvement in FEV1 at 4 h.ResultsMean 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)].ConclusionHomozygosity 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.