Possible role of the 4G/5G polymorphism of the plasminogen activator inhibitor 1 gene in the development of asthma

Abstract

findings show that PAI-1 is closely associated with fibrosis and the accumulation of ECM after lung injury or inflammation. We previously reported that the PAI1 gene is induced in lung mast cells in asthmatic subjects.3 These findings suggest that PAI-1 could contribute to tissue remodeling and subsequent fibrosis in asthma. The PAI1 gene has variation in the promoter region on the basis of a single guanosine insertion-deletion (5G or 4G),4,5 and the *4G allele is correlated with increased plasma PAI-1 levels.5,6 In vitro experiments have initially shown that the *5G allele contains an additional binding site for a protein likely related to the nuclear factor κB group of transcription factors, and this binding site is absent in the *4G allele.4 After stimulation with IL-1, HepG2 cells transfected with the *4G allele produce 6 times more PAI-1 mRNA than those with the *5G allele. These data suggest a functional role of the 4G/5G polymorphism in the response to cytokines, with the *4G allele being associated with enhanced gene expression. In the present study we demonstrate that the *4G allele is preferentially transmitted to asthmatic children. These data suggest a possible role of the PAI1 gene and the 4G polymorphism in the pathophysiology of asthma.