Analysis of the 4G/5G variant of the PAI1 (SERPINE1) gene - diagnostics of recurrent miscarriages and thrombophilia

Testing the PAI1 gene

In physiological conditions, when the blood vessel wall is damaged, a number of processesre activated to stop bleeding. Components in the blood plasma are involved, including platelets and proteins (clotting factors). The transformations lead to the formation of a clot from a substance called fibrin. Once the vessel wall has regenerated, it is necessary to start dissolving it – fibrinolysis. In addition to dissolving the clot, the process of fibrinolysis is extremely important in wound healing, but also in the course of inflammation and cancer.

Thrombophilia is a type of clotting disorder and refers to a condition when the blood has an increased tendency to form clotsor a reduced ability to dissolve them. There are a number of extrinsic risk factors for thrombophilia, including prolonged immobilization, smokingcigarettes, and taking hormonal drugss. However, another large group of causes are congenital, genetically determined diseases thatre likely to cause abnormal (too much or too little) amounts of clotting factorsand other substances that regulate their function.

One of the genesrs thats impact on thrombophilia has been proven in scientific studies is PAI-1. This gene encodes the synthesis of a compound thatrs responsible for inhibiting proteins thatre involved in clot dissolution. If there is an increase in PAI-1 levels, it more strongly inhibits the proteins, which slows down the process of clot breakdown and increases the propensity for clogging (occlusion) of the vessels.

Polymorphism, i.e., the occurrence of multiple variants of the same gene in a population, also applies to the gene encoding the PAI-1 protein. In someindividuals, variants are detected thatcause increased levels of this compound in the blood. These individuals are particularlylly at risk for cardiovascular diseaseb and thromboembolism. Abnormal levels of PAI-1 also adversely affect the formation of the placenta, which can result in problems with or complications of pregnancy.

Each year, many peopleb die from vascular obstructions, whichre resulting in a number of complications that reduce quality of life. Genetic testing to determine polymorphisms within the PAI1 gene can helpc identify the cause of episodesof thrombosis in the past or assess the risk of future episodes.

Pai1 gene testing– when to perform?

The test is ordered to diagnose the rs cause of thrombophilia – increased clot formationin the vessels. If a young person (<50 years old) has a history of unexplained thromboembolic complications–that occurred without other risk factors and in unusual locations (e.g., abdominal vessels), either in themselves or in their family, genetic analysis can help–identify the cause.

Thrombophilia can be used to diagnose thromboembolism

It can be supplemented by testing for mutations in other known genes responsible for increased risk of thrombosis such as factor II, V (Leiden), or MTHFR.

Also, the test can be ordered as an adjunct in assessing the risk of thrombosis in patients with coronary artery disease or in diagnosing causes of infertility and obstetric complications.

Testing of the PAI1 gene – who should perform it?

Persons with symptoms of thrombophilic thromboembolism:

• unilateral painl and swelling of the lower limb (venous thrombosis)
• bl in the chest, shortness of breath, hemoptysis, cough (pulmonary embolism)
• heart attack
• mstroke

Women with a history of obstetric failure:

• recurrent miscarriages of unexplained cause
• intrauterine death and stillbirth
• pre-eclampsia,
• pre-eclampsia
• pregnancy hypertension
• intrauterine fetal growth restriction