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).


CONCLUSIONS
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.
Pampuch
A
A
Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
Kowal
K
K
Bodzenta-Lukaszyk
A
A
Di Castelnuovo
A
A
Chyczewski
L
L
Donati
M B
MB
Iacoviello
L
L
D000328:Adult; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000150:complications / Q000235:genetics; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D039981:Pyroglyphidae / Q000276:immunology*
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human