CE MarkEER053032

32 Tests - 675 Promoter 4G/5G


The PAI-1 enzyme is one of the major inhibitors of the plasminogen’s system. It is a 50-KDa glycoprotein belonging to the so-called serpin’s super-family of the serin-protease inhibitors. Recent studies have been shown a strong association between high levels of PAI-1 in the plasma of middle age individuals, and an increased risk of myocardial infarction.

Furthermore, in young men the increased activity of PAI-1 affects the incidence of cardiac ischemia. The fibrinolytic process, nowadays better defined as the plasminogen system, is the final step of the haemostasis that allows clot removal once the blood-vessel wall has been repaired. The plasminogen protein possesses several functional domains, such as: the protease domain and five homologous domains, called Kringle-domains, that contain binding sites for the fibrin and the cell surface.

The plasminogen is an inactive pro-enzyme that, once converted into the active serin-protease plasmin, cleaves fibrin and the components of the extra-cellular matrix allowing the repair of the blood vessel’s wall. Two physiologic activators of the plasminogen have been recently identified: the tPA, a tissue activator, and the uPA, a urokinase-like activator. PAI-1 inhibits both plasminogen’s inhibitors. The plasminogen system’s inhibitors belonging to the serpin’s super-family display a specific reactive site, in their carboxy-terminal region, that is cleaved by the targeted enzyme in this way finally resulting into an enzyme-inhibitor inactive complex.

It has been suggested that the 4G/5G polymorphism is involved in the regulation of its own expression. This polymorphism, due to the deletion/insertion of a singe nucleotide in the promoter region at position 675, results into two different alleles with a sequence of 4 or 5 guanosine. Interestingly, it has been observed that homozygous individuals for the guanosine deletion (4G) have elevated PAI-1 levels, whereas homozygous individuals for the guanosine insertion (5G) display PAI-1 levels reduced of 20-25% and increased plasmin activity.