Mechanisms of allergy and clinical immunologyPLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline
Section snippets
Methods
For additional information, see this article's Online Repository at www.jacionline.org.
Phase 1: microsatellite analysis identifies an asthma/lung function locus
The clinical characteristics of all cohorts are shown in Tables I and II. The Southampton and Nottingham cohorts were used in phase 1. Multipoint linkage analysis using the Nottingham cohort highlighted a broad region of suggestive linkage for FEV1 spanning region 1, peak LOD 1.4, P = .006 around D19S900/178 (Fig 1, A). No significant linkage was observed in the Southampton cohort (data not shown). Association with asthma or lung function–related phenotypes was observed in the Southampton
Discussion
We have used linkage and association analyses to define further an asthma susceptibility region of 14.4 Mbps and identify the PLAUR gene as a potential asthma susceptibility gene. Importantly, we have shown the same direction of effect between allelic variants and asthma, BHR, and FEV1, particularly in the 3′ region, intron 3, and 5′ region, in more than 1 cohort. SNPs identified were associated with plasma/serum PLAUR levels, providing a link between genetic association and protein levels of
References (32)
- et al.
A second-generation genomewide screen for asthma-susceptibility alleles in a founder population
Am J Hum Genet
(2000) - et al.
Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. populations: collaborative study on the genetics of asthma
Am J Hum Genet
(2001) - et al.
Possible role of the 4G/5G polymorphism of the plasminogen activator inhibitor 1 gene in the development of asthma
J Allergy Clin Immunol
(2001) - et al.
Genome-wide search for atopy susceptibility genes in Dutch families with asthma
J Allergy Clin Immunol
(2002) - et al.
The receptor for urokinase-type plasminogen activator is expressed by keratinocytes at the leading edge during re-epithelialization of mouse skin wounds
J Invest Dermatol
(1994) - et al.
Sputum cathelicidin, urokinase plasminogen activation system components, and cytokines discriminate cystic fibrosis, COPD, and asthma inflammation
Chest
(2005) Gene by environment interaction in asthma
Curr Allergy Asthma Rep
(2006)- et al.
Genetics of asthma: what's new?
A genome-wide search for asthma susceptibility loci in ethnically diverse populations. The Collaborative Study on the Genetics of Asthma (CSGA)
Nat Genet
(1997)- et al.
Genome-wide search for asthma susceptibility loci in a founder population
Hum Mol Genet
(1998)
Clustering patterns of LOD scores for asthma-related phenotypes revealed by a genome-wide screen in 295 French EGEA families
Hum Mol Genet
Genome screen for asthma and related phenotypes in the French EGEA study
Am J Respir Crit Care Med
Genomewide screen for pulmonary function in 200 families ascertained for asthma
Am J Respir Crit Care Med
Linkage to atopy on chromosome 19 in north-eastern Italian families with allergic asthma
Clin Exp Allergy
The urokinase-type-plasminogen-activator receptor (CD87) is a pleiotropic molecule
Eur J Biochem
uPAR: a versatile signalling orchestrator
Nat Rev Mol Cell Biol
Cited by (73)
Mast cell chymase affects the functional properties of primary human airway fibroblasts: Implications for asthma
2022, Journal of Allergy and Clinical ImmunologyCitation Excerpt :A profound increase in the output of soluble uPAR was also confirmed by ELISA analysis (Fig 3, G). uPAR is a cell membrane–bound receptor for uPA and is known to have a complex association with lung pathologies, including asthma.36-40 For example, uPAR release by inflammatory cells of the lamina propria is elevated in asthmatic conditions.40
Genome-wide interaction study of gene-by-occupational exposures on respiratory symptoms
2019, Environment InternationalCitation Excerpt :Serase-1B is known to interact with glycosaminoglycans (GAGs), which maintain lung structure and function, modulate the inflammatory response, influence tissue repair and remodeling, and protect against injury in various respiratory diseases (Okumura et al., 2006). Serase-1B and urokinase-type plasminogen activator (uPA) receptor can efficiently activate uPA, which is involved in epithelial repair and airway remodeling, and is associated with asthma susceptibility, bronchial hyperresponsiveness, and decline in lung function (Barton et al., 2009). Occupational exposure to mineral dust is a well-known risk factor for reduced lung growth and COPD (Cohen et al., 2016; Mehta et al., 2012) of which dyspnea is one of the main symptoms.
Elevated PLAUR is observed in the airway epithelium of asthma patients and blocking improves barrier integrity
2023, Clinical and Translational AllergyObese asthma phenotypes display distinct plasma biomarker profiles
2023, Clinical and Translational Allergy
I.S. is supported by the Medical Research Council (New Investigator Award), and the Dutch family studies were supported by The Netherlands Asthma Foundation. The Southampton Asthma Family Cohort was originally recruited in collaboration with Genome Therapeutics Corp and Schering-Plough.
Disclosure of potential conflict of interest: I. Sayers has received research support from the Medical Research Council UK. N. Maniatis has received research support from the Fellowship from the Medical School, University of Southampton. I. P. Hall has received research support from Medical Research Council UK, Asthma UK, and GlaxoSmithKline/Novartis Pharma and has served as an expert witness regarding medical negligence. J. W. Holloway has received research support from the Medical Research Council UK and Asthma UK. The rest of the authors have declared that they have no conflict of interest.
- ∗
These authors contributed equally to this work.