Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/8599
Title: PLAUR polymorphisms and lung function in UK smokers
Authors: Stewart, Ceri E.
Hall, Ian P.
Parker, Stuart G.
Moffat, Miriam F.
Wardlaw, Andrew J.
Connolly, Martin J.
Ruse, Charlotte
Sayers, Ian
First Published: 31-Oct-2009
Publisher: BioMed Central Ltd
Citation: BMC Medical Genetics, 2009, 10:112
Abstract: Background: We have previously identified Urokinase Plasminogen Activator Receptor (PLAUR) as an asthma susceptibility gene. In the current study we tested the hypothesis that PLAUR single nucleotide polymorphisms (SNPs) determine baseline lung function and contribute to the development of Chronic Obstructive Pulmonary Disease (COPD) in smokers. Methods: 25 PLAUR SNPs were genotyped in COPD subjects and individuals with smoking history (n = 992). Linear regression was used to determine the effects of polymorphism on baseline lung function (FEV[subscript 1], FEV[subscript 1]/FVC) in all smokers. Genotype frequencies were compared in spirometry defined smoking controls (n = 176) versus COPD cases (n = 599) and COPD severity (GOLD stratification) using logistic regression. Results: Five SNPs showed a significant association (p < 0.01) with baseline lung function; rs2302524(Lys220Arg) and rs2283628(intron 3) were associated with lower and higher FEV[subscript 1] respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV[subscript 1]/FVC ratio. rs740587 was also protective for COPD susceptibility and rs11668247 was protective for COPD severity although no allele dose relationship was apparent. Interestingly, several of these associations were driven by male smokers not females. Conclusion: This study provides tentative evidence that the asthma associated gene PLAUR also influences baseline lung function in smokers. However the case-control analyses do not support the conclusion that PLAUR is a major COPD susceptibility gene in smokers. PLAUR is a key serine protease receptor involved in the generation of plasmin and has been implicated in airway remodelling.
DOI Link: 10.1186/1471-2350-10-112
ISSN: 1471-2350
Links: http://www.biomedcentral.com/1471-2350/10/112
http://hdl.handle.net/2381/8599
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2009 Stewart et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Appears in Collections:Published Articles, Dept. of Infection, Immunity and Inflammation

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