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Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease Aminuddin, Farzian; Hackett, Tillie-Louise; Stefanowicz, Dorota; Saferali, Aabida; Paré, Peter D.; Gulsvik, Amund; Bakke, Per; Cho, Michael H.; Litonjua, Augusto; Lomas, David A.; Anderson, Wayne H.; Beaty, Terri H.; Silverman, Edwin K.; Sandford, Andrew J.

Abstract

Background: Due to the pleiotropic effects of nitric oxide (NO) within the lungs, it is likely that NO is a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to test for association between single nucleotide polymorphisms (SNPs) in three NO synthase (NOS) genes and lung function, as well as to examine gene expression and protein levels in relation to the genetic variation. Methods: One SNP in each NOS gene (neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3)) was genotyped in the Lung Health Study (LHS) and correlated with lung function. One SNP (rs1800779) was also analyzed for association with COPD and lung function in four COPD case–control populations. Lung tissue expression of NOS3 mRNA and protein was tested in individuals of known genotype for rs1800779. Immunohistochemistry of lung tissue was used to localize NOS3 expression. Results: For the NOS3 rs1800779 SNP, the baseline forced expiratory volume in one second in the LHS was significantly higher in the combined AG + GG genotypic groups compared with the AA genotypic group. Gene expression and protein levels in lung tissue were significantly lower in subjects with the AG + GG genotypes than in AA subjects. NOS3 protein was expressed in the airway epithelium and subjects with the AA genotype demonstrated higher NOS3 expression compared with AG and GG individuals. However, we were not able to replicate the associations with COPD or lung function in the other COPD study groups. Conclusions: Variants in the NOS genes were not associated with lung function or COPD status. However, the G allele of rs1800779 resulted in a decrease of NOS3 gene expression and protein levels and this has implications for the numerous disease states that have been associated with this polymorphism.

Item Metadata

Title
Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease
Creator
Aminuddin, Farzian; Hackett, Tillie-Louise; Stefanowicz, Dorota; Saferali, Aabida; Paré, Peter D.; Gulsvik, Amund; Bakke, Per; Cho, Michael H.; Litonjua, Augusto; Lomas, David A.; Anderson, Wayne H.; Beaty, Terri H.; Silverman, Edwin K.; Sandford, Andrew J.
Contributor
James Hogg iCAPTURE Centre (University of British Columbia)
Publisher
BioMed Central
Date Issued
2013-11-06
Description
Background: Due to the pleiotropic effects of nitric oxide (NO) within the lungs, it is likely that NO is a significant factor in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to test for association between single nucleotide polymorphisms (SNPs) in three NO synthase (NOS) genes and lung function, as well as to examine gene expression and protein levels in relation to the genetic variation. Methods: One SNP in each NOS gene (neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3)) was genotyped in the Lung Health Study (LHS) and correlated with lung function. One SNP (rs1800779) was also analyzed for association with COPD and lung function in four COPD case–control populations. Lung tissue expression of NOS3 mRNA and protein was tested in individuals of known genotype for rs1800779. Immunohistochemistry of lung tissue was used to localize NOS3 expression. Results: For the NOS3 rs1800779 SNP, the baseline forced expiratory volume in one second in the LHS was significantly higher in the combined AG + GG genotypic groups compared with the AA genotypic group. Gene expression and protein levels in lung tissue were significantly lower in subjects with the AG + GG genotypes than in AA subjects. NOS3 protein was expressed in the airway epithelium and subjects with the AA genotype demonstrated higher NOS3 expression compared with AG and GG individuals. However, we were not able to replicate the associations with COPD or lung function in the other COPD study groups. Conclusions: Variants in the NOS genes were not associated with lung function or COPD status. However, the G allele of rs1800779 resulted in a decrease of NOS3 gene expression and protein levels and this has implications for the numerous disease states that have been associated with this polymorphism.
Subject
Chronic obstructive pulmonary disease; Nitric oxide synthase; Polymorphism; Gene expression
Genre
Article
Type
Text
Language
eng
Date Available
2016-02-03
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0223913
URI
http://hdl.handle.net/2429/56858
Affiliation
Non UBC; Medicine, Faculty of; Medicine, Department of; Science, Faculty of; Microbiology and Immunology, Department of; Anesthesiology, Pharmacology and Therapeutics, Department of
Citation
BMC Pulmonary Medicine. 2013 Nov 06;13(1):64
Publisher DOI
10.1186/1471-2466-13-64
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Aminuddin et al.; licensee BioMed Central Ltd.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)