Fibrinolytic gene polymorphism and ischemic stroke
Artikel i vetenskaplig tidskrift, 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

Författare

Katarina Jood

Göteborgs universitet

Per Ladenvall

Göteborgs universitet

Anna Tjärnlund-Wolf

Göteborgs universitet

Claes Ladenvall

Göteborgs universitet

Maria Andersson

Göteborgs universitet

Staffan Nilsson

Göteborgs universitet

Chalmers, Matematiska vetenskaper, matematisk statistik

Christian Blomstrand

Göteborgs universitet

Christina Jern

Göteborgs universitet

Stroke

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

Vol. 36 2077-81

Ämneskategorier

Dermatologi och venereologi

PubMed

16179568