An Insertion/Deletion polymorphism in the promoter region of the plasminogen activator inhibitor-1 gene is associated with plasma levels but not with stroke risk in the elderly

Abstract

The purpose of the present study was to examine the effects of an insertion/deletion (ins/del) polymorphism in the promoter region of the plasminogen activator inhibitor-1 (PAI-1) gene on plasma PAI-1 antigen and activity levels and on stroke risk in the elderly. The ins/del genotype and PAI-1 antigen and activity plasma levels were determined in 177 patients with ischemic stroke (mean age, 75 years) and 93 healthy elderly subjects (mean age, 74 years). There was no difference in the frequencies of the ins and del alleles between stroke patients and healthy elderly subjects. The del/del genotype was associated with the highest plasma PAI-1 antigen levels in the healthy subjects: those with the ins/ins genotype had 36% lower plasma PAI-1 antigen levels than those with the del/del genotype (effect of genotype, P=0.3). In contrast, the ins/del genotype was not associated with plasma PAI-1 antigen and activity levels in 89 patients who had a stroke less than 10 days before blood sampling. However, an association of ins/del genotype with plasma PAI-1 activity levels could be demonstrated in 88 other patients more than 5 months after the stroke. This may suggest that PAI-1 metabolism is temporarily perturbed after a stroke. The present data suggest that an ins/del polymorphism in the PAI-1 promoter region affects plasma PAI-1 levels but has little or no effect on stroke risk in the elderly.