GLCCI1 rs37973 is associated with the response of adrenal hormone to inhaled corticosteroids in asthma

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 μg, 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 FEV(1) (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 [ΔEPI(AA+AG) = 6.843 (9.26) pg/ml, n(AA+AG) = 26; ΔEPI(GG) = −1.666 (6.52) pg/ml, n(GG) = 4; P = 0.018] and cortisol concentration [ΔCOR(AA+AG) = 0.3040 (0.21) ng/ml, n(AA+AG) = 26; ΔCOR(GG) = −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. TRIAL REGISTRATION: ChiCTR-RCC-13003634 www.chictr.org.cn. Active since September 27, 2013.