NFE2L2 polymorphisms, mortality, and metabolism in the general population
The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) gene regulates transcription of enzymes involved in cellular detoxification and lipids homeostasis. NFE2L2 is associated with pathophysiology of atherosclerosis and chronic obstructive pulmonary disease (COPD). Therefore we studied the...
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American Physiological Society
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060038/ |
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pubmed-40600382014-08-06 NFE2L2 polymorphisms, mortality, and metabolism in the general population Figarska, Sylwia M. Vonk, Judith M. Boezen, H. Marike General Interest The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) gene regulates transcription of enzymes involved in cellular detoxification and lipids homeostasis. NFE2L2 is associated with pathophysiology of atherosclerosis and chronic obstructive pulmonary disease (COPD). Therefore we studied the relation between NFE2L2 and all-cause, cardiovascular, and COPD mortality and its associations with triglyceride and cholesterol levels. We genotyped five tagging single nucleotide polymorphisms (SNPs) (rs4243387, rs2364723, rs13001694, rs1806649, and rs6726395) in NFE2L2 in 1,390 subjects from the Vlagtwedde-Vlaardingen cohort. Participants were examined in 1989/1990 and followed up till the vital status evaluation on December 31st, 2008. Associations between SNPs and mortality were estimated by Cox proportional hazards regression, and associations between SNPs and triglyceride and cholesterol levels were tested with linear regression. After 18 yr, 284 (20.4%) subjects had died, 107 from cardiovascular disease and 20 from COPD. Minor allele carriers of rs13001694 had a significantly reduced risk of all-cause mortality compared with wild types: hazard ratio (HR) 0.8 [95% confidence interval (CI) 0.6 to 1.0]. Minor allele carriers of rs2364723 had significantly reduced risk of cardiovascular mortality: HR = 0.5 (95% CI: 0.3–0.7). This result was consistent in stratified analyses: females 0.4 (0.2–0.7), males 0.6 (0.3–0.9), never smokers 0.5 (0.2–1.1), ever smokers 0.5 (0.3–0.8). Minor allele carriers of rs1806649 had a markedly reduced COPD mortality: HR = 0.3 (95% CI: 0.1–0.9). Rs2364723 was associated with lower triglyceride levels. None of the SNPs was associated with cholesterol levels. This study shows for the first time that NFE2L2 is associated with reduced risk of all-cause, cardiovascular and COPD mortality in humans. American Physiological Society 2014-05-01 2014-06-15 /pmc/articles/PMC4060038/ /pubmed/24790085 http://dx.doi.org/10.1152/physiolgenomics.00178.2013 Text en Copyright © 2014 the American Physiological Society Licensed under Creative Commons Attribution CC-BY 3.0 (http://creativecommons.org/licenses/by/3.0/deed.en_US) : the American Physiological Society. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Figarska, Sylwia M. Vonk, Judith M. Boezen, H. Marike |
| spellingShingle |
Figarska, Sylwia M. Vonk, Judith M. Boezen, H. Marike NFE2L2 polymorphisms, mortality, and metabolism in the general population |
| author_facet |
Figarska, Sylwia M. Vonk, Judith M. Boezen, H. Marike |
| author_sort |
Figarska, Sylwia M. |
| title |
NFE2L2 polymorphisms, mortality, and metabolism in the general population |
| title_short |
NFE2L2 polymorphisms, mortality, and metabolism in the general population |
| title_full |
NFE2L2 polymorphisms, mortality, and metabolism in the general population |
| title_fullStr |
NFE2L2 polymorphisms, mortality, and metabolism in the general population |
| title_full_unstemmed |
NFE2L2 polymorphisms, mortality, and metabolism in the general population |
| title_sort |
nfe2l2 polymorphisms, mortality, and metabolism in the general population |
| description |
The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or NRF2) gene regulates transcription of enzymes involved in cellular detoxification and lipids homeostasis. NFE2L2 is associated with pathophysiology of atherosclerosis and chronic obstructive pulmonary disease (COPD). Therefore we studied the relation between NFE2L2 and all-cause, cardiovascular, and COPD mortality and its associations with triglyceride and cholesterol levels. We genotyped five tagging single nucleotide polymorphisms (SNPs) (rs4243387, rs2364723, rs13001694, rs1806649, and rs6726395) in NFE2L2 in 1,390 subjects from the Vlagtwedde-Vlaardingen cohort. Participants were examined in 1989/1990 and followed up till the vital status evaluation on December 31st, 2008. Associations between SNPs and mortality were estimated by Cox proportional hazards regression, and associations between SNPs and triglyceride and cholesterol levels were tested with linear regression. After 18 yr, 284 (20.4%) subjects had died, 107 from cardiovascular disease and 20 from COPD. Minor allele carriers of rs13001694 had a significantly reduced risk of all-cause mortality compared with wild types: hazard ratio (HR) 0.8 [95% confidence interval (CI) 0.6 to 1.0]. Minor allele carriers of rs2364723 had significantly reduced risk of cardiovascular mortality: HR = 0.5 (95% CI: 0.3–0.7). This result was consistent in stratified analyses: females 0.4 (0.2–0.7), males 0.6 (0.3–0.9), never smokers 0.5 (0.2–1.1), ever smokers 0.5 (0.3–0.8). Minor allele carriers of rs1806649 had a markedly reduced COPD mortality: HR = 0.3 (95% CI: 0.1–0.9). Rs2364723 was associated with lower triglyceride levels. None of the SNPs was associated with cholesterol levels. This study shows for the first time that NFE2L2 is associated with reduced risk of all-cause, cardiovascular and COPD mortality in humans. |
| publisher |
American Physiological Society |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060038/ |
| _version_ |
1612102214388547584 |