High levels of plasminogen activator inhibitor type I (PAI-I) have been implicated as a risk factor for cardiovascular disease, but its precise role remains controversial. The 4G allele of the PAI-I 4G/5G promoter polymorphism is associated with higher levels of PAI-I. We studied the relationship between ischemic stroke and the PAI-I 4G/5G polymorphism and PAI-I 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-I 4G/5G polymorphism and PAI-I 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-I 4G/SG 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% Cl: 0.6-1.8).The relative risk of ischemic stroke associated with the level of PAI-I in the upper quartile was 0.73 (95%Cl: 0.4 to 1.4). Neither the PAI-I 4G/5G polymorphism nor the PAI-I antigen level is a strong risk factor for ischemic stroke.

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doi.org/10.1160/TH04-09-0560, hdl.handle.net/1765/72475
Thrombosis and Haemostasis: international journal for vascular biology and medicine
Department of Neurology

van Goor, M.-L., Gómez García, E., Leebeek, F., Brouwers, G. J., Koudstaal, P., & Dippel, D. (2005). The plasminogen activator inhibitor (PAI-1) 4G/5G promoter polymorphism and PAI-1 levels in ischemic stroke. A case-control study. Thrombosis and Haemostasis: international journal for vascular biology and medicine, 93(1), 92–96. doi:10.1160/TH04-09-0560