|
Plasminogen-Activator-Inhibitor-1 4G/5G (PAI-1 4G/5G)
Insertion / Deletion polymorphism
Plasminogen-Activator-Inhibtor-1 is an important regulator of hemostasis. The PAI-1 gene promoter contains a 4G / 5G insertion/deletion polymorphism. The 4G variant causes enhanced transcription and is associated with enhanced plasma levels of PAI-1 protein and with a procoagulant state. Importantly, the PAI-1 gene promoter 4G variant increases the thrombotic risk when other risk factors like the factor V Leiden mutation or antiphospholipid antibodies are present. Clinical associations have been described with thrombosis (1-4), preeclampsia (5) , prognosis of polytrauma and sepsis (6,7) and risk of myocardial infarction (8). The urokinase plasminogen activator-PAI system and the PAI-1 4G/5G polymorphism were also shown to play a role in the development of more aggressive colon and breast cancer (9,10).
References : Thrombosis and Preeclampsia
(1) Balta G. et al. PAI-1 gene 4G/5G genotype: A risk factor for thrombosis in vessels of internal organs. Am J Hematol 2002 Oct;71(2):89-93
(PMID: 12353306)<Abstract>
(2) Akar N. et al. Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish deep vein thrombotic patients with and without FV1691 G-A.
Thromb Res 2000 Feb 15;97(4):227-30
(PMID: 10674409) <Abstract>
(3) Visanji J.M. et al. Influence of the -675 4G/5G dimorphism of the plasminogen activator inhibitor 1 promoter on thrombotic risk in patients with factor V Leiden.
Br J Haematol 2000 Jul;110(1):135-8
(PMID: 10930990)<Abstract>
(4) Tassies D. et al. The 4G/5G polymorphism of the type 1 plasminogen activator inhibitor gene and thrombosis in patients with antiphospholipid syndrome.
Arthritis Rheum 2000 Oct;43(10):2349-58
(PMID: 11037896)<Abstract>
(5) Glueck C.J.et al. Genetic hypofibrinolysis in complicated pregnancies.
Obstet Gynecol 2001 Jan;97(1):44-8
(PMID: 11152905) <Abstract>
References : Prognosis of Polytrauma and Sepsis
(6) Hermans P.W.et al. 4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene and outcome of meningococcal disease. Lancet 1999 Aug 14;354(9178):556-60
(PMID: 10470700)<Abstract>
(7) Menges T et al. Plasminogen-activator-inhibitor-1 4G/5G promoter polymorphism and prognosis of severely injured patients. Lancet 2001 Apr 7;357(9262):1096-7 (PMID: 11297964)<Abstract>
References : Myocardial Infarction
(8) Yoshiji Yamada et al. Prediction of the Risk of Myocardial Infarction from Polymorphisms in Candidate Genes. NEJM 2002, 347:1916-1923
References : Colon and Breast Cancer
(9) Loktionov A. et al. Plasminogen activator inhibitor-1 gene polymorphism and colorectal cancer risk and prognosis. Cancer Lett 2003 Jan 28;189(2):189-96
(PMID: 12490312)<Abstract>
(10) Alvarez-Millan J.J. et al. PAI-1 promoter polymorphism modulates uPA-PAI complex accumulation by breast cancer cells. Oncology 2002;62(3):286-90
(PMID: 12065877)<Abstract>
|
