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Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

BACKGROUND: Understanding the environmental and genetic risk factors of accelerated lung function decline in the general population is a first step in a prevention strategy against the worldwide increasing respiratory pathology of chronic obstructive pulmonary disease (COPD). Deficiency in antioxida...

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Autores principales: Imboden, Medea, Downs, Sara H, Senn, Oliver, Matyas, Gabor, Brändli, Otto, Russi, Erich W, Schindler, Christian, Ackermann-Liebrich, Ursula, Berger, Wolfgang, Probst-Hensch, Nicole M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781067/
https://www.ncbi.nlm.nih.gov/pubmed/17217536
http://dx.doi.org/10.1186/1465-9921-8-2
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author Imboden, Medea
Downs, Sara H
Senn, Oliver
Matyas, Gabor
Brändli, Otto
Russi, Erich W
Schindler, Christian
Ackermann-Liebrich, Ursula
Berger, Wolfgang
Probst-Hensch, Nicole M
author_facet Imboden, Medea
Downs, Sara H
Senn, Oliver
Matyas, Gabor
Brändli, Otto
Russi, Erich W
Schindler, Christian
Ackermann-Liebrich, Ursula
Berger, Wolfgang
Probst-Hensch, Nicole M
author_sort Imboden, Medea
collection PubMed
description BACKGROUND: Understanding the environmental and genetic risk factors of accelerated lung function decline in the general population is a first step in a prevention strategy against the worldwide increasing respiratory pathology of chronic obstructive pulmonary disease (COPD). Deficiency in antioxidative and detoxifying Glutathione S-transferase (GST) gene has been associated with poorer lung function in children, smokers and patients with respiratory diseases. In the present study, we assessed whether low activity variants in GST genes are also associated with accelerated lung function decline in the general adult population. METHODS: We examined with multiple regression analysis the association of polymorphisms in GSTM1, GSTT1 and GSTP1 genes with annual decline in FEV1, FVC, and FEF(25–75 )during 11 years of follow-up in 4686 subjects of the prospective SAPALDIA cohort representative of the Swiss general population. Effect modification by smoking, gender, bronchial hyperresponisveness and age was studied. RESULTS: The associations of GST genotypes with FEV1, FVC, and FEF(25–75 )were comparable in direction, but most consistent for FEV1. GSTT1 homozygous gene deletion alone or in combination with GSTM1 homozygous gene deletion was associated with excess decline in FEV1 in men, but not women, irrespective of smoking status. The additional mean annual decline in FEV1 in men with GSTT1 and concurrent GSTM1 gene deletion was -8.3 ml/yr (95% confidence interval: -12.6 to -3.9) relative to men without these gene deletions. The GSTT1 effect on the FEV1 decline comparable to the observed difference in FEV1 decline between never and persistent smoking men. Effect modification by gender was statistically significant. CONCLUSION: Our results suggest that genetic GSTT1 deficiency is a prevalent and strong determinant of accelerated lung function decline in the male general population.
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spelling pubmed-17810672007-01-25 Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study Imboden, Medea Downs, Sara H Senn, Oliver Matyas, Gabor Brändli, Otto Russi, Erich W Schindler, Christian Ackermann-Liebrich, Ursula Berger, Wolfgang Probst-Hensch, Nicole M Respir Res Research BACKGROUND: Understanding the environmental and genetic risk factors of accelerated lung function decline in the general population is a first step in a prevention strategy against the worldwide increasing respiratory pathology of chronic obstructive pulmonary disease (COPD). Deficiency in antioxidative and detoxifying Glutathione S-transferase (GST) gene has been associated with poorer lung function in children, smokers and patients with respiratory diseases. In the present study, we assessed whether low activity variants in GST genes are also associated with accelerated lung function decline in the general adult population. METHODS: We examined with multiple regression analysis the association of polymorphisms in GSTM1, GSTT1 and GSTP1 genes with annual decline in FEV1, FVC, and FEF(25–75 )during 11 years of follow-up in 4686 subjects of the prospective SAPALDIA cohort representative of the Swiss general population. Effect modification by smoking, gender, bronchial hyperresponisveness and age was studied. RESULTS: The associations of GST genotypes with FEV1, FVC, and FEF(25–75 )were comparable in direction, but most consistent for FEV1. GSTT1 homozygous gene deletion alone or in combination with GSTM1 homozygous gene deletion was associated with excess decline in FEV1 in men, but not women, irrespective of smoking status. The additional mean annual decline in FEV1 in men with GSTT1 and concurrent GSTM1 gene deletion was -8.3 ml/yr (95% confidence interval: -12.6 to -3.9) relative to men without these gene deletions. The GSTT1 effect on the FEV1 decline comparable to the observed difference in FEV1 decline between never and persistent smoking men. Effect modification by gender was statistically significant. CONCLUSION: Our results suggest that genetic GSTT1 deficiency is a prevalent and strong determinant of accelerated lung function decline in the male general population. BioMed Central 2007 2007-01-11 /pmc/articles/PMC1781067/ /pubmed/17217536 http://dx.doi.org/10.1186/1465-9921-8-2 Text en Copyright © 2007 Imboden et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Imboden, Medea
Downs, Sara H
Senn, Oliver
Matyas, Gabor
Brändli, Otto
Russi, Erich W
Schindler, Christian
Ackermann-Liebrich, Ursula
Berger, Wolfgang
Probst-Hensch, Nicole M
Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study
title Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study
title_full Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study
title_fullStr Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study
title_full_unstemmed Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study
title_short Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study
title_sort glutathione s-transferase genotypes modify lung function decline in the general population: sapaldia cohort study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781067/
https://www.ncbi.nlm.nih.gov/pubmed/17217536
http://dx.doi.org/10.1186/1465-9921-8-2
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