GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients

• Published in: Scientific reports 2017-02, Vol.7 (1), p.42552-42552, Article 42552
• Main Authors: Lei, Yuan, Gao, Yiping, Chen, Jinkun, Li, Miao, Wu, Xiaomei, Ning, Qin, Zhao, Jianping, Xiong, Weining, Xu, Yongjian, Xie, Jungang
• Format: Article
• Language: English
• Subjects: 13/31; 45/22; 45/77; 631/154/436/434; 692/699/1785/4037; Administration, Inhalation; Adrenal Cortex Hormones - pharmacology; Adrenal Cortex Hormones - therapeutic use; Aged; Aged, 80 and over; Alleles; Apoptosis; Apoptosis - drug effects; Chronic obstructive pulmonary disease; Cigarette smoke; Corticoids; Corticosteroids; Dexamethasone; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Female; Flow cytometry; Fluticasone; Follow-Up Studies; Genetic Predisposition to Disease; Genotype; Genotype & phenotype; Genotypes; Glucocorticoids; Humanities and Social Sciences; Humans; Leukocytes (neutrophilic); Lung diseases; Male; Middle Aged; multidisciplinary; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; Obstructive lung disease; Propionic acid; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - genetics; Receptors, Glucocorticoid - genetics; Respiratory function; Respiratory Function Tests; Respiratory therapy; Risk Factors; Salmeterol; Science; Smoking; Transcription; Treatment Outcome
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep42552

Inhaled corticosteroids (ICSs) are widely prescribed in chronic obstructive pulmonary disease (COPD). However, little is known about predictors of ICSs therapeutic response. To investigate whether the variation in glucocorticoid-induced transcript 1 ( GLCCI1 ) rs37973 is associated with ICS efficacy. A total of 204 clinically stable COPD patients were recruited and administered to inhaled fluticasone propionate/salmeterol combination (500/50 ug, twice daily) for 24 weeks. We genotyped the functional rs37973 and mainly assessed its effects on changes in lung function. In vitro , neutrophils isolated from parts of patients were incubated with various concentrations of dexamethasone (0, 10 −6  M and 10 −4  M) in the presence or absence of cigarette smoke extract, apoptosis was then assessed by flow cytometry. Patients with the homozygous GG genotype (increases of 15.3 ± 33.2 mL) had significantly poorer improvement in FEV 1 than those with the AA (92.7 ± 29.6 mL; p