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dc.contributor.authorAminuddin, Farzianen_US
dc.contributor.authorHackett, Tillie-Louiseen_US
dc.contributor.authorStefanowicz, Dorotaen_US
dc.contributor.authorSaferali, Aabidaen_US
dc.contributor.authorParé, Peter D.en_US
dc.contributor.authorGulsvik, Amunden_US
dc.contributor.authorBakke, Peren_US
dc.contributor.authorCho, Michael H.en_US
dc.contributor.authorLitonjua, Augusto A.en_US
dc.contributor.authorLomas, David A.en_US
dc.contributor.authorAnderson, Wayne H.en_US
dc.contributor.authorBeaty, Terri H.en_US
dc.contributor.authorSilverman, Edwin K.en_US
dc.contributor.authorSandford, Andrew J.en_US
dc.date.accessioned2014-08-27T07:45:14Z
dc.date.available2014-08-27T07:45:14Z
dc.date.issued2013-11-06eng
dc.identifier.issn1471-2466
dc.identifier.urihttps://hdl.handle.net/1956/8351
dc.description.abstractBackground: 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.en_US
dc.language.isoengeng
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/eng
dc.subjectChronic obstructive pulmonary diseaseeng
dc.subjectNitric oxide synthaseeng
dc.subjectPolymorphismeng
dc.subjectGene expressioneng
dc.titleNitric oxide synthase polymorphisms, gene expression and lung function in chronic obstructive pulmonary diseaseen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2013-11-14T20:01:31Z
dc.description.versionpublishedVersionen_US
dc.rights.holderFarzian Aminuddin et al.; licensee BioMed Central Ltd.
dc.rights.holderCopyright 2013 Aminuddin et al.; licensee BioMed Central Ltd.
dc.source.articlenumber64
dc.identifier.doihttps://doi.org/10.1186/1471-2466-13-64
dc.identifier.cristin1117048
dc.source.journalBMC Pulmonary Medicine
dc.source.4013


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