PAI-1 Gene Mutation
(CAD, Ischemic Stroke, Venous Thrombosis, Osteonecrosis)
Plasminogen Activator Inhibitor-1 (PAI-1) is the major inhibitor of
fibrinolysis. When PAI-1 is high, fibrinolytic activity is depressed, and
there is increased risk for arterial and venous thrombosis.
PAI-1 is a significant, independent risk factor for coronary artery disease
and ischemic stroke
It is also a major independent risk factor for venous thrombosis, including
The 4G allele of a recently described common 4/5 Guanine tract (4G/5G)
polymorphism in the PAI-1 gene promotor region is associated with
higher plasma PAI-1 activity.
1. Dawson. S.J., B. Wiman, A. Hamsten, et al.., (1993) The two allele
sequences of a common polymorphism in the promotor of the
plasminogen activator inhibitor-1 (PAl-1) gene respond differenfly to
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increase in basal transcription of the plasminogen activator inhibitor-1
gene is associated with myocardial infarction. Proc. Natl. Acad. Sci. USA
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type 1 plasminogen activator inhibitor gene expression in atherosclerotic
human arteries. Proc. Natl. Acad. Sci. USA 89:6998-7002.
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its role in thrombotic disease. Thromb. and Haemost. 74:71-76.
5. Glueck, C.J., H.I. Glueck, M. Welch et al. (1994) Familial idiopathic
osteonecrosis mediated by familial hypofibrinolysis with high levels of
plasminogen activator inhibitor. Thromb. and Haemost. 71:195-198.
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Moore, L. Sieve-Smith and T. Tracy (2000) The 4G/5G polymorphism of
the hypofibrinolytic plasminogen activator inhibitor type I gene: An
independent risk factor for serious pregnancy complications.
8. Glueck, C.J. M.J. Kupferminc, R.N. Fontaine, P. Wang, B.B. Weksler
and A. Eldor. (2001) Genetic hypofibrinolysis in complicated
pregnancies. Obstet. and Gynecol. 97:44-8.
6. Glueck, C.J., H.I. Glueck, L. Mieczkowski, et al. (1993) Familial high
plasminogen activator inhibitor with hypofibrinolysis, a new
pathophysiologic cause of osteonecrosis? Thromb. and Haemost.
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