The 4G/4G Plasminogen Activator Inhibitor-1 Genotype Is Associated With Frequent Recurrence of Acute Otitis Media

Abstract

Plasminogen activator inhibitor-1 counterregulates cell migration, adhesion, and tissue repair. The PAI1 4G/5G promoter polymorphism has an effect on expression levels of PAI1. After a first acute otitis media episode, children are at increased risk for a next episode. Because the PAI1 4G allele is associated with higher plasminogen activator inhibitor-1 production and, hence, decreased tissue repair, we hypothesize that this allele may contribute to increased recurrence of acute otitis media. The PAI1 4G/5G polymorphism was genotyped in 348 Dutch children aged 1 to 7 years who were suffering from recurrent acute otitis media and participating in a randomized, controlled trial and 463 healthy control subjects, representative of the general population. No significant difference in PAI1 genotype distribution between the whole acute otitis media group and control subjects was observed. However, children with the PAI1 4G/4G genotype had an increased risk of more frequent acute otitis media episodes compared with those who were homozygous for the 5G variant, also after correction for cofactors. This finding was attributable to children <4 years of age. Our findings suggest that the PAI1 4G/4G genotype is associated with an increased risk for the otitis-prone condition, potentially because of impaired healing after a previous otitis media episode.