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Open Access 01-12-2013 | Research article

Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease

Authors: Farzian Aminuddin, Tillie-Louise Hackett, Dorota Stefanowicz, Aabida Saferali, Peter D Paré, Amund Gulsvik, Per Bakke, Michael H Cho, Augusto Litonjua, David A Lomas, Wayne H Anderson, Terri H Beaty, Edwin K Silverman, Andrew J Sandford

Published in: BMC Pulmonary Medicine | Issue 1/2013

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2466/13/64/prepub

Title: Nitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary disease
Authors: Farzian Aminuddin
Tillie-Louise Hackett
Dorota Stefanowicz
Aabida Saferali
Peter D Paré
Amund Gulsvik
Per Bakke
Michael H Cho
Augusto Litonjua
David A Lomas
Wayne H Anderson
Terri H Beaty
Edwin K Silverman
Andrew J Sandford
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: BMC Pulmonary Medicine / Issue 1/2013
Electronic ISSN: 1471-2466
DOI: https://doi.org/10.1186/1471-2466-13-64

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