title: GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients.
abstract: 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, 10-6M and 10-4M) 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 FEV1than those with the AA (92.7 ± 29.6 mL; p < 0.001) or AG (59.4 ± 26.9 mL; p < 0.001) genotypes after 24-week treatment. In vitro, dexamethasone had less inhibitory effect of neutrophil apoptosis on GG genotype, which further validated the presence of mutant allele 'G' might negatively affect glucocorticoid responsiveness irrespective of smoking status. The GG genotype of rs37973 may associated with decreased ICSs efficacy in Chinese COPD patients.
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Acadia Junior High School, Winnipeg, Manitoba, R3T 3B3, Canada.
authors.forename: Jinkun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Weining
authors.initials: W
authors.lastname: Xiong
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
authors.forename: Jungang
authors.initials: J
authors.lastname: Xie
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017209:Apoptosis / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012129:Respiratory Function Tests; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; C561807:GLCCI1 protein, human; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone