The plasminogen activator inhibitor (PAI-1) 4G/5G promoter polymorphism and PAI-1 levels in ischemic stroke. A case-control study.

High levels of plasminogen activator inhibitor type 1 (PAI-1) have been implicated as a risk factor for cardiovascular disease, but its precise role remains controversial. The 4G allele of the PAI-1 4G/5G promoter polymorphism is associated with higher levels of PAI-1. We studied the relationship between ischemic stroke and the PAI-1 4G/5G polymorphism and PAI-1 antigen levels. We performed a case-control study among patients aged 18-75 years with first ischemic stroke, confirmed by CT. All patients were screened for cardiovascular risk factors, cardiac disorders and large vessel disease. We excluded patients with a definite non-atherosclerotic cause of the stroke and patients using oral anticoagulants. Population-controls were age -and sex-matched, without a history of stroke, and of the Caucasian race. Venous blood samples were taken for PAI-1 4G/5G polymorphism and PAI-1 level one week after stroke. We included 124 patients and 125 controls. Mean age was 56 yrs (range 18 to 75 yrs). Sixty one patients (50%) and 58 (47%) controls were heterozygous for the PAI-1 4G/5G polymorphism. The homozygous 4G/4G genotype was found in 33 patients (27%) and in 36 controls (29%). The odds ratio of ischemic stroke associated with 4G-carriers versus 5G/5G homozygotes was 1.0 (95% CI: 0.6-1.8). The relative risk of ischemic stroke associated with the level of PAI-1 in the upper quartile was 0.73 (95%CI: 0.4 to 1.4). Neither the PAI-1 4G/5G polymorphism nor the PAI-1 antigen level is a strong risk factor for ischemic stroke.