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Fibrinolytic gene polymorphism and ischemic stroke

Journal article
Authors Katarina Jood
Per Ladenvall
Anna Tjärnlund-Wolf
Claes Ladenvall
Maria Andersson
Staffan Nilsson
Christian Blomstrand
Christina Jern
Published in Stroke
Volume 36
Issue 10
Pages 2077-81
ISSN 00392499
Publication year 2005
Published at Cardiovascular Institute
Department of Mathematical Sciences, Mathematical Statistics
Institute of Clinical Neurosciences
Pages 2077-81
Language en
Keywords Adolescent, Adult, Aged, Alleles, Brain/metabolism, Brain Ischemia/*genetics, Case-Control Studies, Cerebrovascular Accident/diagnosis/*genetics, Female, Fibrinolysis/*genetics, Genotype, Homozygote, Humans, Male, Middle Aged, Models, Statistical, Multivariate Analysis, Myocardial Infarction/genetics, Myocardium/metabolism, Odds Ratio, Plasminogen Activator Inhibitor 1/blood/genetics, *Polymorphism, Genetic, Regression Analysis, Research Support, Non-U.S. Gov't, Risk Factors, Thrombosis/diagnosis/genetics, Tissue Plasminogen Activator/blood/genetics, Transcription, Genetic
Subject categories Dermatology and Venereal Diseases


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.

Page Manager: Webmaster|Last update: 9/11/2012

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