Fibrinolytic gene polymorphism and ischemic stroke
Journal article, 2005

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.

*Polymorphism

Humans

Multivariate Analysis

Myocardium/metabolism

Thrombosis/diagnosis/genetics

Research Support

Models

Tissue Plasminogen Activator/blood/genetics

Male

Non-U.S. Gov't

Genotype

Female

Genetic

Risk Factors

Brain/metabolism

Odds Ratio

Adult

Myocardial Infarction/genetics

Cerebrovascular Accident/diagnosis/*genetics

Regression Analysis

Case-Control Studies

Genetic

Aged

Transcription

Plasminogen Activator Inhibitor 1/blood/genetics

Homozygote

Brain Ischemia/*genetics

Fibrinolysis/*genetics

Alleles

Middle Aged

Adolescent

Statistical

Author

Katarina Jood

University of Gothenburg

Per Ladenvall

University of Gothenburg

Anna Tjärnlund-Wolf

University of Gothenburg

Claes Ladenvall

University of Gothenburg

Maria Andersson

University of Gothenburg

Staffan Nilsson

University of Gothenburg

Chalmers, Mathematical Sciences, Mathematical Statistics

Christian Blomstrand

University of Gothenburg

Christina Jern

University of Gothenburg

Stroke

0039-2499 (ISSN) 1524-4628 (eISSN)

Vol. 36 10 2077-81

Subject Categories

Dermatology and Venereal Diseases

PubMed

16179568

More information

Created

10/7/2017