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

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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. [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.
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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.

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基金编号: 81570033 81570047 81470227 81370145 81370156 2015CB553403 2013BAI09B00 2016YFC1303900 2016YFC1304700 IRT_14R20

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出版当年[2016]版:
大类 | 2 区 综合性期刊
小类 | 2 区 综合性期刊
最新[2025]版:
大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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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.
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