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
osteonecrosis.
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.
References:
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
interleukin-l in HepG2 cells. J. Biol. Chem. 268: 10739-45.
2. Eriksson, P. B. Kallin, F. M. Van't Hoffi et al. (1995) Allele-specific
increase in basal transcription of the plasminogen activator inhibitor-1
gene is associated with myocardial infarction. Proc. Natl. Acad. Sci. USA
92:1851-5.
3. Schneiderman, J. M.S. Sawdey, M.R Keeton, et al. (1992) Increase
type 1 plasminogen activator inhibitor gene expression in atherosclerotic
human arteries. Proc. Natl. Acad. Sci. USA 89:6998-7002.
4. Wiman, B. (1995) Plasminogen activator inhibitor-1 (PAI-1) in plasma:
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.
7. Glueck, C.J. H. Phillips, D. Cameron, P. Wang, R.N. Fontaine, S.K.
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.
Metabolism 49:845-52.
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.
69:460-5.
For more information go to National Center for Biotechnology Information
(NCBI).
Most abstracts and many full length articles can be printed from this web site.
www.ncbi.nlm.nih.gov/
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