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 10 2077-81Ämneskategorier
Dermatologi och venereologi
PubMed
16179568