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 2077-81Subject Categories
Dermatology and Venereal Diseases
PubMed
16179568