4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and insertion/deletion polymorphism of the tissue-type plasminogen activator gene inatherothrombotic stroke
Co. Bang et al., 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and insertion/deletion polymorphism of the tissue-type plasminogen activator gene inatherothrombotic stroke, CEREB DIS, 11(4), 2001, pp. 294-299
Background and Purpose: Decreased fibrinolytic capacity due to increased pl
asminogen activator inhibitor-1 (PAI-1) activity and decreased tissue-type
plasminogen activator (t-PA) activity has been associated with hypertension
or atherothrombotic disorders. The aims of this study were to observe asso
ciations of the genetic polymorphism for PAI-1 and t-PA with hypertension a
nd atherothrombotic stroke, and to elucidate whether impaired fibrinolytic
activity in atherothrombotic stroke was related to atherothrombosis per se
or to other risk factors such as hypertension. Methods: Patients with ather
othrombotic stroke (n = 60), hypertension (n = 100), and control subjects (
n = 100) were enrolled. We genotyped all subjects for 4G/5G polymorphism in
the promoter region of the PAI-1 gene and the Alu-repeat insertion/deletio
n (I/D) polymorphism in intron h of the t-PA gene by polymerase chain react
ion and endonuclease digestion. Results: The frequency of th e 4G/4G genoty
pe of PAI-1 was significanlty higher in the atherothombotic stroke patients
than the control subjects (41.7 versus 21%; p = 0.005), but not in the hyp
ertensive subjects. There was a significant association between 4G/4G genot
ype of PAI-1 and atherothrombotic stroke (adjusted odds ratio = 3.11, 95% c
onfidence interval 1.18-8.15), adjusting for age, sex, total cholesterol, l
ow-density lipoprotein, triglyceride, and body mass index. However, the num
ber of the I/I genotype of t-PA in the atherothrombotic stroke or hypertens
ive patients was virtually identical to the control subjects. Conclusion: O
ur results suggest that the 4G/4G genotype of the PAI-1 gene is significant
ly associated with an increased risk of atherothrombotic stroke. This findi
ng also supports that impaired fibrinolytic activity in atherothrombotic st
roke is related to atherothrombosis per se, but not to hypertension, one of
the most important risk factors of atherothrombotic stroke. Copyright (C)
2001 S. Karger AG, Basel.