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(Stroke. 2005;36:2077.)
© 2005 American Heart Association, Inc.

Original Contributions

Fibrinolytic Gene Polymorphism and Ischemic Stroke

Katarina Jood, MD; Per Ladenvall, MD, PhD; Anna Tjärnlund-Wolf, PhD; Claes Ladenvall, MSc; Maria Andersson, MSc; Staffan Nilsson, PhD; Christian Blomstrand, MD, PhD Christina Jern, MD, PhD

From the Institute of Clinical Neuroscience (K.J., A.T.-W., C.L., C.B., C.J.) and the Clinical Experimental Research Laboratory, Cardiovascular Institute (P.L., M.A.), the Sahlgrenska Academy at Göteborg University; the Department of Clinical Genetics, Sahlgrenska University Hospital/Östra (A.T.-W., C.L., C.J.); the Department of Mathematical Statistics (S.N.), Chalmers University of Technology, Göteborg, Sweden.

Correspondence to Dr Christina Jern, Institute of Clinical Neuroscience, the Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital/Sahlgrenska, S-413 45 Göteborg, Sweden. E-mail christina.jern{at}neuro.gu.se

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.

Key Words: ischemic stroke subtypes • plasminogen activator inhibitor type 1 • polymorphism • tissue-type plasminogen activator

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