PLAUR polymorphisms and lung function in UK smokers.
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(1), FEV(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(1) respectively. rs740587(-22346), rs11668247(-20040) and rs344779(-3666) in the 5'region were associated with increased FEV(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.


CONCLUSIONS
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.
Stewart
Ceri E
CE
Division of Therapeutics & Molecular Medicine, Nottingham Respiratory Biomedical Research Unit, University Hospital of Nottingham, Nottingham, UK. ceri.stewart@nottingham.ac.uk
Hall
Ian P
IP
Parker
Stuart G
SG
Moffat
Miriam F
MF
Wardlaw
Andrew J
AJ
Connolly
Martin J
MJ
Ruse
Charlotte
C
Sayers
Ian
I
D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics* / Q000503:physiopathology; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics*; D012129:Respiratory Function Tests; D012907:Smoking / Q000235:genetics*; D006113:United Kingdom
C524898:PLAUR protein, human; D055293:Receptors, Urokinase Plasminogen Activator