PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline

Barton, Sheila J.; Koppelman, Gerard H.; Vonk, Judith M.; Browning, Claudia A.; Nolte, Ilja M.; Stewart, Ceri E.; Bainbridge, Susan; Mutch, Stacey; Rose-Zerilli, Matthew; Postma, Dirkje S.; Maniatis, Nikolas; Henry, Amanda; Hall, Ian P.; Holgate, Stephen T.; Tighe, Patrick J.; Holloway, John W.; Sayers, Ian

doi:10.1016/j.jaci.2009.03.014

Cited by 76 publications

(91 citation statements)

References 36 publications

(38 reference statements)

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“…Environmental conditions, such as poor indoor and outdoor air quality, are risk factors of asthma, but they are much more clearly related to the provocation of asthma attacks and to asthma severity than they are to the prevalence of asthma (Strachan, 2000). However, genetic factors play an important role in the development of asthma, and the heritability of asthma has been estimated to vary between 36 and 79% (Koppelman, 2006;Barton et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the ORM1-like 3 gene associated with childhood asthma in a Chinese population

Yang

Huang²,

Li³

et al. 2012

Genet. Mol. Res.

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ABSTRACT. Single nucleotide polymorphism (SNP)-based genome-wide association studies have revealed that polymorphisms of the ORM1-like 3 (ORMDL3) gene are associated with childhood asthma. We investigated genetic associations of SNPs in and around the ORMDL3 gene with childhood asthma in a Chinese population. Genomic DNA was extracted from peripheral venous blood drawn from 152 subjects with childhood asthma and from 190 control subjects. SNP genotyping was performed with the MassARRAY system (Sequenom) by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Among the six SNPs, only the genotype frequencies of rs7216389 were significantly different between asthmatic children and controls. Asthmatic children had a significantly higher frequency of T alleles [odds ratio (OR) = 1.653, 95% confidence interval (95%CI) = 1.170-2.333] in rs7216389, than controls. The TT genotype of rs7216389 was found to be a significant risk factor for childhood asthma by logistic regression analysis (OR = 1.704, 95%CI = 1.105-©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 11 (4): 4646-4653 (2012) Polymorphisms of ORMDL3 and childhood asthma 4647 2.628). There was no significant association between the TT genotype of rs7216389 and clinical features of childhood asthma. We conclude that the ORMDL3 gene influences childhood asthma and that the TT genotype of the rs7216389 polymorphism is associated with childhood asthma in the Chinese population.

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Section: Introductionmentioning

confidence: 99%

Single nucleotide polymorphisms in the ORM1-like 3 gene associated with childhood asthma in a Chinese population

Yang

Huang²,

Li³

et al. 2012

Genet. Mol. Res.

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“…A recent linkage and association study identified the plasma urokinase plasminogen activator receptor (PLAUR) gene in chromosome 19q13.1-3 as a potential asthma susceptibility gene [60]. Polymorphisms in the PLAUR gene were associated with asthma, AHR, FEV1 and plasma levels of PLAUR (also known as uPAR) [60].…”

Section: Discussionmentioning

confidence: 99%

“…Polymorphisms in the PLAUR gene were associated with asthma, AHR, FEV1 and plasma levels of PLAUR (also known as uPAR) [60]. PLAUR interacts with urokinase plasminogen activator, resulting in enhanced activation of cell-bound plasminogen [61] and, therefore, plays a role in PAS.…”

Section: Discussionmentioning

confidence: 99%

SERPINE1 -675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

Dijkstra¹,

Postma

Bruinenberg³

et al. 2011

European Respiratory Journal

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Asthma is characterised by chronic airway inflammation and remodelling, which can be (partially) suppressed by inhaled corticosteroids (ICSs). Plasminogen activator inhibitor-1, encoded by the SERPINE1 gene, is the key inhibitor of the plasminogen activator system, which affects tissue repair and remodelling.We studied associations between a functional SERPINE1 -675 4G/5G promoter polymorphism and asthma development, severity and response to ICSs.Longitudinal cohorts of 281 asthmatics and their nonasthmatic spouses, and the general population (n51,390) were studied. No significant associations were found with asthma development and immunoglobulin (Ig)E levels, or with forced expiratory volume in 1 s (FEV1) in nonasthmatic controls. Asthmatic subjects carrying the SERPINE1 5G allele had higher IgE and lower lung function levels at follow-up, lower maximally attained lung function levels, and faster lung function decline compared with individuals with the 4G/4G genotype. ICS treatment showed an immediate improvement in FEV1 in asthmatics carrying the 5G allele. However, these asthmatics still had the fastest rate of FEV1 decline after initiating ICS treatment. Finally, the 5G allele was associated with a lower prevalence of complete asthma remission at follow-up.These findings suggest that SERPINE1 is not an asthma susceptibility gene, but rather affects the severity, progression and long-term ICS response in asthma.

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“…A good example is the recent protein eQTL analyses of serum urokinase plasminogen activator receptor (suPAR) levels (Portelli et al, 2014). uPAR has been identified as an asthma susceptibility gene (Barton et al, 2009) and has been shown to be differentially expressed in the airways (Stewart, Nijmeh, Brightling, & Sayers, 2012) and blood (Portelli et al, 2014) in asthma patients. The receptor exists as a glycosyl-phosphatidylinositol (GPI)-linked receptor and is involved in a wide range of functions including migration, proliferation and adhesion and is also involved in fibrinolysis (Portelli et al, 2014).…”

Section: Protein Eqtl Can Provide Novel Insight Beyond Cis and Trans mentioning

confidence: 99%

Translating Lung Function Genome-Wide Association Study (GWAS) Findings

Kheirallah

Miller

Hall

et al. 2016

Advances in Genetics

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PLAUR polymorphisms are associated with asthma, PLAUR levels, and lung function decline

Cited by 76 publications

References 36 publications

Single nucleotide polymorphisms in the ORM1-like 3 gene associated with childhood asthma in a Chinese population

Single nucleotide polymorphisms in the ORM1-like 3 gene associated with childhood asthma in a Chinese population

SERPINE1 -675 4G/5G polymorphism is associated with asthma severity and inhaled corticosteroid response

Translating Lung Function Genome-Wide Association Study (GWAS) Findings

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