PAI-1 -675(4G/5G)

The fibrinolytic system is a mechanism opposed to the coagulation system and in equilibrium with it, in condition of normal blood flux. This system is based on plasminogen, which is converted in plasmin by the tissutal (t-PA) or urokinase (u-PA) plasminogen activator. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of the fibrinolytic system and is produced by a variety of cells like liver cells, platelets, endothelial cells, smooth muscular cells of vessel walls.
PAI -1 is a member of the SERPIN family and binds to the tissutal plasminogen activator (tPA), inhibiting its activation causing a reduction of fibrinolysis. Enhanced levels of this inhibitor have been related to a higher thrombotic risk, both arterial (myocardial infarction and coronary disease) and venous (thromboembolism), especially in smokers and hypertensive subjects. In facts, its plasmatic level is increased after surgery and leads to a decrease of fibrinolytic activity which could explain the observed post-operating hypercoagulability. Besides, the balance between plasminogen activators and their inhibitor, would have a major role in the formation of the arterial thrombus after breaking of an atheromatous plaque. High levels of PAI -1 have also been observed during methabolic syndrome, in association with hypertension, obesity, insulin resistance, elevated levels of triglycerides and low concentrations of high density lipoproteins (HDL).
PAI-1 gene presents an insertion/deletion polymorphism (SNP) of a single G (4G/5G) at position -675 from the starting site of the gene, in a regulatory region at the 5` end (promoter). 26% of the population has 4G/4G genotype, 50% is heterozygous (4G/5G) and 24% has 5G/5G genotype. 4G allele has been associated to higher thrombotic risk since it’s related to an increase of transcriptional activity of the gene and increased plasmatic levels of PAI -1, which are 25% higher in case of homozygosity 4G/4G compared to 5G/5G genotype. In fact, it’s reputed that the promotor with 4G mutation is able to bind only one enhancer, while allele 5G can bind both an enhancer and a suppressor. Afterwards, it’s been demonstrated that di PAI -1 promoter exerts a genotype-specific response to triglycerids, with higher levels of PAI -1 in subjects with 4G/4G genotype in presence of high levels of triglycerides. At last, pregnant women with 4G/4G genotype have a bigger incidence of complications during pregnancy and delivery, when compared to 5G/5G women.

The kit is available in sizes from 24, 48 or 72 reactions.

Screening test for: Genetic Thrombophilia

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