Fibrinolytic Gene Polymorphism and Ischemic Stroke

• Published in: Stroke (1970) Vol. 36; no. 10; pp. 2077 - 2081
• Main Authors: Jood, Katarina, Ladenvall, Per, Tjärnlund-Wolf, Anna, Ladenvall, Claes, Andersson, Maria, Nilsson, Staffan, Blomstrand, Christian, Jern, Christina
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.10.2005
• Subjects: Adolescent; Adult; Aged; Alleles; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Brain - metabolism; Brain Ischemia - genetics; Case-Control Studies; Cerebrovascular Accident/diagnosis/genetics; Dermatologi och venereologi; Dermatology and Venereal Diseases; Female; Fibrinolysis - genetics; Genetic; Genotype; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Homozygote; Humans; Male; Medical sciences; Middle Aged; Models, Statistical; Multivariate Analysis; Myocardial Infarction - genetics; Myocardium - metabolism; Nervous system (semeiology, syndromes); Neurology; Non-U.S. Gov't; Odds Ratio; Pharmacology. Drug treatments; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1/blood/genetics; Polymorphism; Polymorphism, Genetic; Regression Analysis; Research Support; Risk Factors; Statistical; Stroke - diagnosis; Stroke - genetics; Thrombosis - diagnosis; Thrombosis - genetics; Thrombosis/diagnosis/genetics; Tissue Plasminogen Activator - blood; Tissue Plasminogen Activator - genetics; Tissue Plasminogen Activator/blood/genetics; Transcription; Transcription, Genetic; Vascular diseases and vascular malformations of the nervous system; ischemic stroke subtypes; Cerebral infarction; Stroke; Nervous system diseases; Serine endopeptidases; Enzyme; Cardiovascular disease; t-Plasminogen activator; Cerebral disorder; plasminogen activator inhibitor type 1; Vascular disease; Peptidases; Plasminogen activator inhibitor 1; Central nervous system disease; Hydrolases; tissue-type plasminogen activator; Cerebrovascular disease; Fibrinolytic; Polymorphism
• ISSN: 0039-2499; 1524-4628; 1524-4628
• DOI: 10.1161/01.STR.0000183617.54752.69

Background and Purpose— The tissue-type plasminogen activator (tPA) −7351C>T and the plasminogen activator inhibitor type 1 (PAI-1) -675 4G >5G polymorphisms influence transcriptional activity. Both variants have been associated with myocardial infarction, with increased risk for the T and 4G allele, respectively. In this study we investigated the possible association between these polymorphisms, the respective plasma protein levels, and ischemic stroke. Methods— In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), 600 patients with acute ischemic stroke aged 18 to 69 years and 600 matched community controls were recruited. Stroke subtype was determined using Trial of Org 10172 in Acute Treatment criteria. Results— There were no associations between individual genetic variants and ischemic stroke. The multivariate-adjusted odds ratio for overall ischemic stroke was 1.11 (95% CI 0.87 to 1.43) for tPA T allele carriers, and 0.84 (95% CI, 0.64 to 1.11) for subjects homozygous for the PAI-1 4G allele. When genotypes were combined, a protective effect for the tPA CC/PAI-1 4G4G genotype combination was observed (odds ratio 0.65, 95% CI 0.43 to 0.98; P <0.05). Plasma levels of tPA and PAI-1 antigen at follow-up were independently associated with overall ischemic stroke. tPA-antigen differed by stroke subtype and was highest among those with large-vessel disease and cardioembolic stroke. Conclusions— Neither the tPA −7351C>T nor the PAI-1 to 675 4G >5G polymorphism showed significant association with ischemic stroke. For the tPA CC/PAI-1 4G4G genotype combination, a protective effect was observed. Collectively, these results are consistent with a more complex role for tPA and PAI-1 in the brain as compared with the heart.