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PLAUR polymorphisms and lung function in UK smokers

By Ceri E. Stewart, Ian P. Hall, Stuart G. Parker, Miriam F. Moffat, Andrew J. Wardlaw, Martin J. Connolly, Charlotte Ruse and Ian Sayers


Background:\ud 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.\ud Methods:\ud 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.\ud Results:\ud 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.\ud Conclusion:\ud 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.Peer-reviewedPublisher Versio

Publisher: BioMed Central Ltd
Year: 2009
DOI identifier: 10.1186/1471-2350-10-112
OAI identifier:

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  1. (1996). A: Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. doi
  2. (1996). Bobik A: Regulation and role of urokinase plasminogen activator in vascular remodelling. Clin Exp Pharmacol Physiol doi
  3. (2003). Bodzenta-Lukaszyk A: The plasmin system in airway remodeling. Thromb Res doi
  4. (2002). Carmeliet P: uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol doi
  5. (2007). Carrozzi L: Definition, epidemiology and natural history of COPD. Eur Respir J doi
  6. (2002). F-J: Urokinase receptor surface expression regulates monocyte adhesion in acute myocardial infarction. Blood
  7. (1995). F: A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene. Blood
  8. (1998). Fujinaga K: The Ets-1 and Ets-2 transcription factors activate the promoters for invasion-associated urokinase and collagenase genes in response to epidermal growth factor. doi
  9. (2005). G: ets-1 is transcriptionally up-regulated by H2O2 via an antioxidant response element. doi
  10. (2008). Gene expression profiling in patients with chronic obstructive pulmonary disease and lung cancer. Am J Respir Crit Care Med doi
  11. (2006). Genetic association analysis of functional impairment in chronic obstructive pulmonary disease. Am J Respir Crit Care Med doi
  12. (2007). Genetic determinants of emphysema distribution in the national emphysema treatment trial. Am J Respir Crit Care Med doi
  13. (2002). Genomewide linkage analysis of quantitative spirometric phenotypes in severe early-onset chronic obstructive pulmonary disease. doi
  14. (2007). Gonias SL: uPAR induces epithelial-mesenchymal transition in hypoxic breast cancer cells. The Journal of cell biology doi
  15. (2009). Hines OJ: Transcriptional regulation of urokinase-type plasminogen activator receptor by hypoxia-inducible factor 1 is crucial for invasion of pancreatic and liver cancer. doi
  16. Holgate S: Genetics of Asthma: what's new? doi
  17. (2007). I: Salmeterol and cytokines modulate inositol-phosphate signalling in human airway smooth muscle cells via regulation at the receptor locus. Respir Res doi
  18. (2007). Macnee W: Cardiovascular risk in chronic obstructive pulmonary disease. Respirology doi
  19. (1998). Medcalf RL: The urokinase-type-plasminogen-activator receptor (CD87) is a pleiotropic molecule. doi
  20. (2005). MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics doi
  21. (2004). Peripheral lung remodelling in asthma and chronic obstructive pulmonary disease. doi
  22. (1988). Plasminogen activator inhibitors--a review. Enzyme
  23. (2009). PLAUR polymorphisms are associated with asthma, PLAUR levels and lung function decline. J Allergy Clin Immunol doi
  24. (2006). RA: The genetics of chronic obstructive pulmonary disease. Respir Res doi
  25. (2005). RB: Sputum cathelicidin, urokinase plasminogen activation system components, and cytokines discriminate cystic fibrosis, COPD, and asthma inflammation. Chest doi
  26. (2009). Sayers I: Characterisation of urokinase plasminogen activator receptor variants in human airway and peripheral cells. doi
  27. (2007). Sex differences in severe pulmonary emphysema. Am J Respir Crit Care Med doi
  28. (2007). SG: The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two large populations. Am J Respir Crit Care Med doi
  29. (2006). Shear stress induces hepatocyte PAI-1 gene expression through cooperative Sp1/Ets-1 activation of transcription. doi
  30. (2002). Siafakas NM: The relationships among hydrogen peroxide in expired breath condensate, airway inflammation, and asthma severity. Chest doi
  31. (2004). Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J doi
  32. (1998). Structural alterations and inflammation of bronchi in asthma.
  33. (2004). The transforming growth factor-beta1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD). Hum Mol Genet
  34. (1997). uPA, uPAR, PAI-1: key intersection of proteolytic, adhesive and chemotactic highways? Immunol Today doi
  35. (2007). Urokinase-type plasminogen activator. doi

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