Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population

Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcr...
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Autor*in:	Siedlinski, Mateusz [verfasserIn] Postma, Dirkje S Boer, Jolanda MA van der Steege, Gerrit Schouten, Jan P Smit, Henriette A Boezen, H Marike

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2009

Schlagwörter:	Chronic Obstructive Pulmonary Disease Complete Linkage Disequilibrium Chronic Obstructive Pulmonary Disease Subject Dutch Cohort Pool Cohort

Anmerkung:	© Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Respiratory research - London : BioMed Central, 2001, 10(2009), 1 vom: 11. Aug.
Übergeordnetes Werk:	volume:10 ; year:2009 ; number:1 ; day:11 ; month:08

Links:	Volltext

DOI / URN:	10.1186/1465-9921-10-73

Katalog-ID:	SPR028509315

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245	1	0	\|a Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population
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520			\|a Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population.
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700	1		\|a Postma, Dirkje S \|4 aut
700	1		\|a Boer, Jolanda MA \|4 aut
700	1		\|a van der Steege, Gerrit \|4 aut
700	1		\|a Schouten, Jan P \|4 aut
700	1		\|a Smit, Henriette A \|4 aut
700	1		\|a Boezen, H Marike \|4 aut
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allfields	10.1186/1465-9921-10-73 doi (DE-627)SPR028509315 (SPR)1465-9921-10-73-e DE-627 ger DE-627 rakwb eng Siedlinski, Mateusz verfasserin aut Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Complete Linkage Disequilibrium (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Dutch Cohort (dpeaa)DE-He213 Pool Cohort (dpeaa)DE-He213 Postma, Dirkje S aut Boer, Jolanda MA aut van der Steege, Gerrit aut Schouten, Jan P aut Smit, Henriette A aut Boezen, H Marike aut Enthalten in Respiratory research London : BioMed Central, 2001 10(2009), 1 vom: 11. Aug. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:10 year:2009 number:1 day:11 month:08 https://dx.doi.org/10.1186/1465-9921-10-73 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 1 11 08
spelling	10.1186/1465-9921-10-73 doi (DE-627)SPR028509315 (SPR)1465-9921-10-73-e DE-627 ger DE-627 rakwb eng Siedlinski, Mateusz verfasserin aut Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Complete Linkage Disequilibrium (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Dutch Cohort (dpeaa)DE-He213 Pool Cohort (dpeaa)DE-He213 Postma, Dirkje S aut Boer, Jolanda MA aut van der Steege, Gerrit aut Schouten, Jan P aut Smit, Henriette A aut Boezen, H Marike aut Enthalten in Respiratory research London : BioMed Central, 2001 10(2009), 1 vom: 11. Aug. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:10 year:2009 number:1 day:11 month:08 https://dx.doi.org/10.1186/1465-9921-10-73 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 1 11 08
allfields_unstemmed	10.1186/1465-9921-10-73 doi (DE-627)SPR028509315 (SPR)1465-9921-10-73-e DE-627 ger DE-627 rakwb eng Siedlinski, Mateusz verfasserin aut Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Complete Linkage Disequilibrium (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Dutch Cohort (dpeaa)DE-He213 Pool Cohort (dpeaa)DE-He213 Postma, Dirkje S aut Boer, Jolanda MA aut van der Steege, Gerrit aut Schouten, Jan P aut Smit, Henriette A aut Boezen, H Marike aut Enthalten in Respiratory research London : BioMed Central, 2001 10(2009), 1 vom: 11. Aug. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:10 year:2009 number:1 day:11 month:08 https://dx.doi.org/10.1186/1465-9921-10-73 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 1 11 08
allfieldsGer	10.1186/1465-9921-10-73 doi (DE-627)SPR028509315 (SPR)1465-9921-10-73-e DE-627 ger DE-627 rakwb eng Siedlinski, Mateusz verfasserin aut Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Complete Linkage Disequilibrium (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Dutch Cohort (dpeaa)DE-He213 Pool Cohort (dpeaa)DE-He213 Postma, Dirkje S aut Boer, Jolanda MA aut van der Steege, Gerrit aut Schouten, Jan P aut Smit, Henriette A aut Boezen, H Marike aut Enthalten in Respiratory research London : BioMed Central, 2001 10(2009), 1 vom: 11. Aug. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:10 year:2009 number:1 day:11 month:08 https://dx.doi.org/10.1186/1465-9921-10-73 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 1 11 08
allfieldsSound	10.1186/1465-9921-10-73 doi (DE-627)SPR028509315 (SPR)1465-9921-10-73-e DE-627 ger DE-627 rakwb eng Siedlinski, Mateusz verfasserin aut Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population 2009 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Complete Linkage Disequilibrium (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Dutch Cohort (dpeaa)DE-He213 Pool Cohort (dpeaa)DE-He213 Postma, Dirkje S aut Boer, Jolanda MA aut van der Steege, Gerrit aut Schouten, Jan P aut Smit, Henriette A aut Boezen, H Marike aut Enthalten in Respiratory research London : BioMed Central, 2001 10(2009), 1 vom: 11. Aug. (DE-627)326646485 (DE-600)2041675-1 1465-993X nnns volume:10 year:2009 number:1 day:11 month:08 https://dx.doi.org/10.1186/1465-9921-10-73 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 10 2009 1 11 08
language	English
source	Enthalten in Respiratory research 10(2009), 1 vom: 11. Aug. volume:10 year:2009 number:1 day:11 month:08
sourceStr	Enthalten in Respiratory research 10(2009), 1 vom: 11. Aug. volume:10 year:2009 number:1 day:11 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Chronic Obstructive Pulmonary Disease Complete Linkage Disequilibrium Chronic Obstructive Pulmonary Disease Subject Dutch Cohort Pool Cohort
isfreeaccess_bool	false
container_title	Respiratory research
authorswithroles_txt_mv	Siedlinski, Mateusz @@aut@@ Postma, Dirkje S @@aut@@ Boer, Jolanda MA @@aut@@ van der Steege, Gerrit @@aut@@ Schouten, Jan P @@aut@@ Smit, Henriette A @@aut@@ Boezen, H Marike @@aut@@
publishDateDaySort_date	2009-08-11T00:00:00Z
hierarchy_top_id	326646485
id	SPR028509315
language_de	englisch
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. 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author	Siedlinski, Mateusz
spellingShingle	Siedlinski, Mateusz misc Chronic Obstructive Pulmonary Disease misc Complete Linkage Disequilibrium misc Chronic Obstructive Pulmonary Disease Subject misc Dutch Cohort misc Pool Cohort Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population
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topic_title	Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population Chronic Obstructive Pulmonary Disease (dpeaa)DE-He213 Complete Linkage Disequilibrium (dpeaa)DE-He213 Chronic Obstructive Pulmonary Disease Subject (dpeaa)DE-He213 Dutch Cohort (dpeaa)DE-He213 Pool Cohort (dpeaa)DE-He213
topic	misc Chronic Obstructive Pulmonary Disease misc Complete Linkage Disequilibrium misc Chronic Obstructive Pulmonary Disease Subject misc Dutch Cohort misc Pool Cohort
topic_unstemmed	misc Chronic Obstructive Pulmonary Disease misc Complete Linkage Disequilibrium misc Chronic Obstructive Pulmonary Disease Subject misc Dutch Cohort misc Pool Cohort
topic_browse	misc Chronic Obstructive Pulmonary Disease misc Complete Linkage Disequilibrium misc Chronic Obstructive Pulmonary Disease Subject misc Dutch Cohort misc Pool Cohort
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title	Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population
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title_full	Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population
author_sort	Siedlinski, Mateusz
journal	Respiratory research
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author_browse	Siedlinski, Mateusz Postma, Dirkje S Boer, Jolanda MA van der Steege, Gerrit Schouten, Jan P Smit, Henriette A Boezen, H Marike
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title_sort	level and course of $ fev_{1} $ in relation to polymorphisms in nfe2l2 and keap1 in the general population
title_auth	Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population
abstract	Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. It additionally shows that NFE2L2 and KEAP1 variations are unlikely to play a role in the longitudinal course of $ FEV_{1} $ in the general population. © Siedlinski et al. 2009. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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title_short	Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population
url	https://dx.doi.org/10.1186/1465-9921-10-73
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author2	Postma, Dirkje S Boer, Jolanda MA van der Steege, Gerrit Schouten, Jan P Smit, Henriette A Boezen, H Marike
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background The metabolism of xenobiotics plays an essential role in smoking related lung function loss and development of Chronic Obstructive Pulmonary Disease. Nuclear Factor Erythroid 2-Like 2 (NFE2L2 or NRF2) and its cytosolic repressor Kelch-like ECH-associated protein-1 (KEAP1) regulate transcription of enzymes involved in cellular detoxification processes and Nfe2l2-deficient mice develop tobacco-induced emphysema. We assessed the impact of Single Nucleotide Polymorphisms (SNPs) in both genes on the level and longitudinal course of Forced Expiratory Volume in 1 second ($ FEV_{1} $) in the general population. Methods Five NFE2L2 and three KEAP1 tagging SNPs were genotyped in the population-based Doetinchem cohort (n = 1,152) and the independent Vlagtwedde-Vlaardingen cohort (n = 1,390). On average 3 $ FEV_{1} $ measurements during 3 surveys, respectively 7 $ FEV_{1} $ measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated $ FEV_{1} $ measurements. Results In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in KEAP1 was associated with a higher $ FEV_{1} $ level (p = 0.02 for an additive effect), and SNP rs2364723 in NFE2L2 was associated with a lower $ FEV_{1} $ level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of KEAP1 or NFE2L2 SNPs with $ FEV_{1} $ decline was observed. Conclusion This is the first genetic study on variations in key antioxidant transcriptional regulators KEAP1 and NFE2L2 and lung function in a general population. It identified 2 SNPs in NFE2L2 and KEAP1 which affect the level of $ FEV_{1} $ in the general population. 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Level and course of $ FEV_{1} $ in relation to polymorphisms in NFE2L2 and KEAP1 in the general population

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