Document Detail


NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease.
MedLine Citation:
PMID:  22693272     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function.
Authors:
Andrew J Sandford; Deepti Malhotra; H Marike Boezen; Mateusz Siedlinski; Dirkje S Postma; Vivien Wong; Loubna Akhabir; Jian-Qing He; John E Connett; Nicholas R Anthonisen; Peter D Paré; Shyam Biswal
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-12
Journal Detail:
Title:  Physiological genomics     Volume:  44     ISSN:  1531-2267     ISO Abbreviation:  Physiol. Genomics     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-03     Completed Date:  2013-03-11     Revised Date:  2013-09-18    
Medline Journal Info:
Nlm Unique ID:  9815683     Medline TA:  Physiol Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  754-63     Citation Subset:  IM    
Affiliation:
UBC James Hogg Research Centre, Providence Heart + Lung Institute, St. Paul's Hospital, Vancouver, British Columbia, Canada. andrew.sandford@hli.ubc.ca
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MeSH Terms
Descriptor/Qualifier:
Adult
Cohort Studies
Demography
Female
Genetic Association Studies
Genetic Predisposition to Disease*
Humans
Linkage Disequilibrium / genetics
Lung / physiopathology*
Male
Middle Aged
NF-E2-Related Factor 2 / genetics*
Polymorphism, Single Nucleotide / genetics*
Pulmonary Disease, Chronic Obstructive / genetics*,  physiopathology*
Respiratory Function Tests
Signal Transduction / genetics*
Smoking / genetics
Grant Support
ID/Acronym/Agency:
5R01HL-064068-04/HL/NHLBI NIH HHS; N01-HR-46002/HR/NHLBI NIH HHS; P01 ES-018176/ES/NIEHS NIH HHS; P30 ES-003819/ES/NIEHS NIH HHS; P50 ES-015903/ES/NIEHS NIH HHS; P50 HL-084945/HL/NHLBI NIH HHS; R01 HL-081205/HL/NHLBI NIH HHS; //Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/NF-E2-Related Factor 2; 0/NFE2L2 protein, human
Comments/Corrections

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