GLCCI1 rs37973 is associated with the response of adrenal hormone to inhaled corticosteroids in asthma
GLCCI1 rs37973 is associated with the response of adrenal hormone to inhaled corticosteroids in asthma
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GLCCI1 rs37973 与哮喘中肾上腺激素对吸入皮质类固醇的反应相关
DOI：
10.1016/j.waojou.2019.100017
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发表时间：
2019-01-01
影响因子：
5.1
通讯作者：
Feng, Juntao
中科院分区：
文献类型：
--
作者：
Xun, Qiufen;Hu, Chengping;Feng, Juntao
背景：先前的研究表明，糖皮质激素诱导的转录物1基因（GLCCI1） rs37973突变基因型与哮喘患者吸入皮质类固醇（ICS）反应不良有关。由于人体气道松弛是由循环肾上腺素调节的，而循环肾上腺素可以通过皮质类固醇增强。目前尚不清楚GLCCI1 rs37973是否与哮喘患者循环肾上腺素和皮质醇浓度相关。本研究的目的是评估这些关系。方法：选取182例哮喘患者和180例健康对照进行研究。30例轻中度哮喘患者接受丙酸氟替卡松（125 μ g, bid）治疗12周。GLCCI1 rs37973基因分型采用iPlex MassARRAY基因分型平台。采用酶联免疫吸附试验（ELISA）试剂盒检测受试者血浆皮质醇和肾上腺素浓度。结果：GLCCI1 rs37973纯合子突变基因型GG血浆肾上腺素浓度较高(中位浓度27.032 pg/ml, n(GG) = 36；中位浓度23.149 pg/ml, n(AA+AG) = 146；P = 0.015)、皮质醇浓度(中位数浓度1.141 ng/ml, n(GG) = 36；中位浓度0.921 ng/ml, n(AA+AG) = 146；P = 0.013)。血浆肾上腺素、皮质醇浓度与FEV1呈正相关（r = 0.889、r = 0.821）。N（哮喘）= 182)。对于接受ICS治疗的哮喘患者，rs37973在隐性模型中与血浆肾上腺素和皮质醇浓度的变化相关（AA+AG vs GG）， GG对肾上腺素浓度的改善较小[Delta EPIAA+AG = 6.843 (9.26) pg/ml, n(AA+AG) = 26；δ EPIGG = -1.666 (6.52) pg/ml, n(GG) = 4；P = 0.018]、皮质醇浓度[δ CORAA+AG = 0.3040 (0.21) ng/ml, n(AA+AG) = 26；δ CORGG = -0.066 (0.24) ng/ml, n(GG) = 4；P = 0.009]。结论：本研究提示GLCCI1 rs37973突变基因型患者ICS反应较差可能与哮喘患者血浆肾上腺素和皮质醇升高幅度较小有关。
Background: Previous studies have demonstrated that glucocorticoid-induced transcript 1 gene (GLCCI1) rs37973 mutant genotype is associated with poor inhaled corticosteroid (ICS) response in asthmatics. As human airway relaxation is regulated by circulation epinephrine, which can be enhanced by corticosteroid. It is unknown whether or not GLCCI1 rs37973 is associated with circulation epinephrine and cortisol concentrations in asthma. The aim of this study is to evaluate these relationships.Methods: A total of 182 asthmatics and 180 healthy controls were recruited for the study. 30 mild-to-moderate asthmatics received fluticasone propionate (125 mu g, bid) treatment for 12 weeks. GLCCI1 rs37973 genotyping was performed with the iPlex MassARRAY genotyping platform. The plasma concentrations of cortisol and epinephrine of each participant were detected by enzyme linked immunosorbent assay (ELISA) kits.Results: GLCCI1 rs37973 homozygotes mutant genotype GG had a higher plasma epinephrine concentration (median concentration 27.032 pg/ml, n(GG) = 36; median concentration 23.149 pg/ml, n(AA+AG) = 146; P = 0.015) and cortisol concentration (median concentration 1.141 ng/ml, n(GG) = 36; median concentration 0.921 ng/ml, n(AA+AG) = 146; P = 0.013). Both epinephrine concentration and cortisol concentration in plasma were positively correlated with FEV1 (r = 0.889 and r = 0.821, respectively. n(asthma) = 182). For asthmatics treated with ICS, rs37973 was associated with change in plasma epinephrine and cortisol concentration in a recessive model (AA + AG vs GG), with GG had less improvement in epinephrine concentration [Delta EPIAA+AG = 6.843 (9.26) pg/ml, n(AA+AG) = 26; Delta EPIGG = -1.666 (6.52) pg/ml, n(GG) = 4; P = 0.018] and cortisol concentration [Delta CORAA+AG = 0.3040 (0.21) ng/ml, n(AA+AG) = 26; Delta CORGG = -0.066 (0.24) ng/ml, n(GG) = 4; P = 0.009].Conclusions: Our study suggested that the poor ICS response in GLCCI1 rs37973 mutant genotype might be related to the less increased amplitudes of plasma epinephrine and cortisol in asthmatic patients.