Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general population
<p>Abstract</p> <p>Background</p> <p>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 Kelc...
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doaj-f90ddfa9477346259e460e597db297522020-11-25T00:55:06ZengBMCRespiratory Research1465-99212009-08-011017310.1186/1465-9921-10-73Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general populationSiedlinski MateuszPostma Dirkje SBoer Jolanda MAvan der Steege GerritSchouten Jan PSmit Henriette ABoezen H Marike<p>Abstract</p> <p>Background</p> <p>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 <it>Nfe2l2</it>-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<sub>1</sub>) in the general population.</p> <p>Methods</p> <p>Five <it>NFE2L2 </it>and three <it>KEAP1 </it>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<sub>1 </sub>measurements during 3 surveys, respectively 7 FEV<sub>1 </sub>measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV<sub>1 </sub>measurements.</p> <p>Results</p> <p>In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in <it>KEAP1 </it>was associated with a higher FEV<sub>1 </sub>level (p = 0.02 for an additive effect), and SNP rs2364723 in <it>NFE2L2 </it>was associated with a lower FEV<sub>1 </sub>level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of <it>KEAP1 </it>or <it>NFE2L2 </it>SNPs with FEV<sub>1 </sub>decline was observed.</p> <p>Conclusion</p> <p>This is the first genetic study on variations in key antioxidant transcriptional regulators <it>KEAP1 </it>and <it>NFE2L2 </it>and lung function in a general population. It identified 2 SNPs in <it>NFE2L2 </it>and <it>KEAP1 </it>which affect the level of FEV<sub>1 </sub>in the general population. It additionally shows that <it>NFE2L2 </it>and <it>KEAP1 </it>variations are unlikely to play a role in the longitudinal course of FEV<sub>1 </sub>in the general population.</p> http://respiratory-research.com/content/10/1/73 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Siedlinski Mateusz Postma Dirkje S Boer Jolanda MA van der Steege Gerrit Schouten Jan P Smit Henriette A Boezen H Marike |
spellingShingle |
Siedlinski Mateusz Postma Dirkje S Boer Jolanda MA van der Steege Gerrit Schouten Jan P Smit Henriette A Boezen H Marike Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general population Respiratory Research |
author_facet |
Siedlinski Mateusz Postma Dirkje S Boer Jolanda MA van der Steege Gerrit Schouten Jan P Smit Henriette A Boezen H Marike |
author_sort |
Siedlinski Mateusz |
title |
Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general population |
title_short |
Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general population |
title_full |
Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general population |
title_fullStr |
Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general population |
title_full_unstemmed |
Level and course of FEV<sub>1 </sub>in relation to polymorphisms in <it>NFE2L2 </it>and <it>KEAP1 </it>in the general population |
title_sort |
level and course of fev<sub>1 </sub>in relation to polymorphisms in <it>nfe2l2 </it>and <it>keap1 </it>in the general population |
publisher |
BMC |
series |
Respiratory Research |
issn |
1465-9921 |
publishDate |
2009-08-01 |
description |
<p>Abstract</p> <p>Background</p> <p>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 <it>Nfe2l2</it>-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<sub>1</sub>) in the general population.</p> <p>Methods</p> <p>Five <it>NFE2L2 </it>and three <it>KEAP1 </it>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<sub>1 </sub>measurements during 3 surveys, respectively 7 FEV<sub>1 </sub>measurements during 8 surveys were present. Linear Mixed Effect models were used to test cross-sectional and longitudinal genetic effects on repeated FEV<sub>1 </sub>measurements.</p> <p>Results</p> <p>In the Vlagtwedde-Vlaardingen cohort SNP rs11085735 in <it>KEAP1 </it>was associated with a higher FEV<sub>1 </sub>level (p = 0.02 for an additive effect), and SNP rs2364723 in <it>NFE2L2 </it>was associated with a lower FEV<sub>1 </sub>level (p = 0.06). The associations were even more significant in the pooled cohort analysis. No significant association of <it>KEAP1 </it>or <it>NFE2L2 </it>SNPs with FEV<sub>1 </sub>decline was observed.</p> <p>Conclusion</p> <p>This is the first genetic study on variations in key antioxidant transcriptional regulators <it>KEAP1 </it>and <it>NFE2L2 </it>and lung function in a general population. It identified 2 SNPs in <it>NFE2L2 </it>and <it>KEAP1 </it>which affect the level of FEV<sub>1 </sub>in the general population. It additionally shows that <it>NFE2L2 </it>and <it>KEAP1 </it>variations are unlikely to play a role in the longitudinal course of FEV<sub>1 </sub>in the general population.</p> |
url |
http://respiratory-research.com/content/10/1/73 |
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