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

BACKGROUNd: Plasminogen activator inhibitor (PAI)-1 plays an important role in inflammation and tissue remodeling. Recently, the -675 4G/5G PAI-1 polymorphism has been linked with asthma. OBJECTIVE: This study was undertaken to evaluate associations of the -675 4G/5G PAI-1 polymorphism with functional and immunologic parameters of newly diagnosed house dust mite-sensitive allergic asthmatics (HDM-AAs). METHODS: This study was performed in 127 HDM-AAs, who responded with at least 20% fall of forced expiratory volume during the first second (FEV(1)) to a bronchial challenge with Dermatophagoides pteronyssinus allergen and during the follow up observation fulfilled GINA criteria for mild-moderate asthma. About 89 healthy control nonatopic subjects (HCs) were used as controls. RESULTS: The frequency of 4G allele was greater in HDM-AAs (0.69; 95% CI: 0.62-0.76) than in HCs (0.55; 95% CI: 0.48-0.62; P = 0.0034). The PAI-1 polymorphism was associated with an increased risk of HDM-AA; adjusted for sex and age odds ratio was 2.62; (95% CI: 1.16-5.92) for 4G/5G genotype and 3.48 (95% CI: 1.54-7.89) for 4G/4G genotype compared with 5G/5G genotype. Total serum immunoglobulin E (tsIgE) level in 4G/4G homozygotes (557 +/- 343 kU/l) was significantly greater than in 5G/5G homozygotes (241 +/- 288 kU/l; P < 0.001). Both nonspecific and allergen-specific bronchial reactivities were greater in 4G/4G homozygotes than in 5G/5G homozygotes. 4G/4G genotype was associated with significantly higher morning plasma PAI-1 concentration in HDM-AAs and HCs. Morning plasma PAI-1 concentration correlated significantly with log(PC20) (r = -0.39; P = 0.0001) and with log(tsIgE) (r = 0.247; P = 0.0117). CONCLUSION: 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.