4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and insertion/deletion polymorphism of the tissue-type plasminogen activator gene in atherothrombotic stroke.
OBJECTIVE
Decreased fibrinolytic capacity due to increased plasminogen 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 associations of the genetic polymorphism for PAI-1 and t-PA with hypertension and 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 atherothrombotic 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/deletion (I/D) polymorphism in intron h of the t-PA gene by polymerase chain reaction and endonuclease digestion.


RESULTS
The frequency of the 4G/4G genotype of PAI-1 was significantly higher in the atherothrombotic stroke patients than the control subjects (41.7 versus 21%; p = 0.005), but not in the hypertensive subjects. There was a significant association between 4G/4G genotype of PAI-1 and atherothrombotic stroke (adjusted odds ratio = 3.11, 95% confidence interval 1.18-8.15), adjusting for age, sex, total cholesterol, low-density lipoprotein, triglyceride, and body mass index. However, the number of the I/I genotype of t-PA in the atherothrombotic stroke or hypertensive patients was virtually identical to the control subjects.


CONCLUSIONS
Our results suggest that the 4G/4G genotype of the PAI-1 gene is significantly associated with an increased risk of atherothrombotic stroke. This finding also supports that impaired fibrinolytic activity in atherothrombotic stroke is related to atherothrombosis per se, but not to hypertension, one of the most important risk factors of atherothrombotic stroke.
Bang
C O
CO
Department of Neurology, Soonchunhyang University Chunan Hospital, Chunan City, Chungnam, Republic of Korea. cobang@schch.co.kr
Park
H K
HK
Ahn
M Y
MY
Shin
H K
HK
Hwang
K Y
KY
Hong
S Y
SY
D000328:Adult; D001161:Arteriosclerosis / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004251:DNA Transposable Elements / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D002542:Intracranial Embolism and Thrombosis / Q000235:genetics*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics; D020521:Stroke / Q000235:genetics*
D004251:DNA Transposable Elements; D017395:Plasminogen Activator Inhibitor 1; D004247:DNA