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

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....

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Autores principales: Lei, Yuan, Gao, Yiping, Chen, Jinkun, Li, Miao, Wu, Xiaomei, Ning, Qin, Zhao, Jianping, Xiong, Weining, Xu, Yongjian, Xie, Jungang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301211/
https://www.ncbi.nlm.nih.gov/pubmed/28186150
http://dx.doi.org/10.1038/srep42552
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author Lei, Yuan
Gao, Yiping
Chen, Jinkun
Li, Miao
Wu, Xiaomei
Ning, Qin
Zhao, Jianping
Xiong, Weining
Xu, Yongjian
Xie, Jungang
author_facet Lei, Yuan
Gao, Yiping
Chen, Jinkun
Li, Miao
Wu, Xiaomei
Ning, Qin
Zhao, Jianping
Xiong, Weining
Xu, Yongjian
Xie, Jungang
author_sort Lei, Yuan
collection PubMed
description 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 < 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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spelling pubmed-53012112017-02-13 GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients Lei, Yuan Gao, Yiping Chen, Jinkun Li, Miao Wu, Xiaomei Ning, Qin Zhao, Jianping Xiong, Weining Xu, Yongjian Xie, Jungang Sci Rep Article 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 < 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. Nature Publishing Group 2017-02-10 /pmc/articles/PMC5301211/ /pubmed/28186150 http://dx.doi.org/10.1038/srep42552 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lei, Yuan
Gao, Yiping
Chen, Jinkun
Li, Miao
Wu, Xiaomei
Ning, Qin
Zhao, Jianping
Xiong, Weining
Xu, Yongjian
Xie, Jungang
GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients
title GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients
title_full GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients
title_fullStr GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients
title_full_unstemmed GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients
title_short GLCCI1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in Chinese chronic obstructive pulmonary disease patients
title_sort glcci1 rs37973: a potential genetic predictor of therapeutic response to inhaled corticosteroids in chinese chronic obstructive pulmonary disease patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5301211/
https://www.ncbi.nlm.nih.gov/pubmed/28186150
http://dx.doi.org/10.1038/srep42552
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