The −675 4G/5G plasminogen activator inhibitor‐1 promoter polymorphism in house dust mite‐sensitive allergic asthma patients

Abstract

These results support the hypothesis linking the 4G/4G PAI-1 genotype with an increased risk of allergic asthma, bronchial hyperreactivity, and increased tsIgE levels.

Plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) in sputum of allergic asthma patients.

“…This is consistent with previous studies performed in humans and in animals [6][7][8][9][10][11][12][13][14][15][16][17]. However, activation of the PAS is not associated exclusively with asthma but its activation could also be demonstrated in other inflammatory lung diseases such as chronic obstructive pulmonary diseases or cystic fibrosis [23].…”

“…We have been already able to demonstrate that in asthmatic patients plasma PAI-1 concentration correlates with baseline FEV 1 and bronchial response to histamine, but it does not correlate with peripheral blood eosinophilia or response to allergen challenge [15,22]. Moreover, in asthmatic patients the -675 4G allele of PAI-1 gene, which is a major genetic determinant of increased PAI-1 synthesis, is associated with lower baseline lung function and greater bronchial reactivity to histamine, suggesting that propensity for increased PAI-1 production is linked with bronchial remodeling [15].…”

“…Moreover, in asthmatic patients the -675 4G allele of PAI-1 gene, which is a major genetic determinant of increased PAI-1 synthesis, is associated with lower baseline lung function and greater bronchial reactivity to histamine, suggesting that propensity for increased PAI-1 production is linked with bronchial remodeling [15]. Furthermore, exposure to an allergen, which leads to increased non-specific bronchial reactivity, induces PAI-1 synthesis [22].…”

“…Also in humans several studies demonstrated association of fibrynolytic system with asthma and bronchial hyperresponsiveness [12][13][14][15][16][17].…”

Concentrations of plasminogen activator inhibitor-1 (PAI-1) and urokinase plasminogen activator (uPA) in induced sputum of asthma patients after allergen challenge.

“…In an animal asthma model either suppression of PAI-1 expression by knockout of the PAI-1 gene or delivery of exogenous uPA leads to decreased airway remodeling and decreased airway hyperresponsiveness [7][8][9]. In humans, genetic variants of uPA and PAI-1 genes are associated with increased risk of allergic asthma [10][11][12][13][14][15]. In clinically stable, mild allergic asthma patients elevated levels of uPA and PAI-1 in induced sputum have recently been demonstrated [16].…”