GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients
单位:[1]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.华中科技大学同济医学院附属同济医院内科学系呼吸与危重症医学科[2]Acadia Junior High School, Winnipeg, Manitoba, R3T 3B3, Canada[3]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.华中科技大学同济医学院附属同济医院感染病研究所感染科
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 FEV1 than 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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570033, 81570047, 81470227, 81370145, 81370156]; National Key Basic Research and Development Program (973 Program)National Basic Research Program of China [2015CB553403]; Chinese Medical Association Research Project [2013BAI09B00]; National Key Technologies RD ProgramNational Key Technology R&D Program [2016YFC1303900, 2016YFC1304700]; Changjiang Scholars and Innovative Research Team in UniversityProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT_14R20]
第一作者单位:[1]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.
通讯作者:
推荐引用方式(GB/T 7714):
lei yuan,gao yiping,chen jinkun,et al.GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients[J].SCIENTIFIC REPORTS.2017,7:doi:10.1038/srep42552.
APA:
lei,yuan,gao,yiping,chen,jinkun,li,miao,wu,xiaomei...&xie,jungang.(2017).GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients.SCIENTIFIC REPORTS,7,
MLA:
lei,yuan,et al."GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients".SCIENTIFIC REPORTS 7.(2017)