bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.25837/HAT.2019.63.13.004bloodjour-105Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWS OF LITERATUREКЛИНИЧЕСКОЕ ЗНАЧЕНИЕ ПОЛИМОРФИЗМА ГЕНОВ ФАКТОРА V И ПРОТРОМБИНАCLINICAL SIGNIFICANCE OF FACTOR V AND PROTHROMBIN GENES POLYMORPHISMhttps://orcid.org/0000-0002-5249-4255КолосковА. В.KoloskovA. V.

д. м. н., доцент, заведующий кафедрой трансфузиологии,

191015, г. Санкт-Петербург

St. Petersburg

Andrei.Koloskov@szgmu.ruhttps://orcid.org/0000-0002-3791-4506ЧерноваЕ. В.ChernovaE. V.

ассистент кафедры трансфузиологии,

191015, г. Санкт-Петербург

St. Petersburg

katerynachernova@mail.ruФГБОУ ВО «Северо-Западный государственный медицинский университет им. И. И. Мечникова» Минздрава РоссииРоссияNorth-Western State Medical University named after I. I. MechnikovRussian Federation201807062019633250257Copyright © Колосков А.В., Чернова Е.В., 20192019Колосков А.В., Чернова Е.В.Koloskov A.V., Chernova E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/105

В 1990-х гг. в качестве генетического субстрата для развития тромбофилии были предложены точечные мутации гена фактора V (FVLeiden) и гена протромбина (FII G20210A). Полиморфизм FVLeiden связывают с развитием резистентности к антикоагулянтному действию протеина C, а полиморфизм FII G20210A с высоким уровнем протромбина в плазме. Частота мутации FVLeiden у здоровых людей европеоидной расы составляет от 2 до 10%, а у пациентов с впервые возникшими тромбозами — 20%. Частота мутации FII G20210A в европеоидной популяции составляет от 1 до 5%, а у пациентов с венозными тромбоэмболиями — от 4 до 18 %. Эти показатели в значительной степени зависят от подбора включаемых в анализ пациентов. Обсуждается связь между генетическим полиморфизмом и развитием тромбозов у женщин во время беременности. Самый высокий риск тромбоза был описан для женщин с гомозиготной мутацией FVLeiden. Изучение взаимодействия активированного протеина C (AПC) и фактора V дало ценную информацию о том, как нарушение этого взаимодействия приводит к тромбозу. Очевидно, что AПC оказывает антикоагулянтное действие за счет инактивации активного фактора V путем расщепления его в точках протеолиза R306 и R506 и преобразования его, таким образом, в неактивную форму. Мутация FVLeiden блокирует этот эффект. У женщин с гетерозиготной мутацией FVLeiden или гетерозиготной мутацией FII G20210A риски тромботических событий существенно ниже. Независимо от генетического полиморфизма, положительный семейный анамнез венозных тромбозов увеличивает риск тромбоэмболических событий во время беременности. Обсуждается связь между генетическим полиморфизмом и нетромботическими осложнениями, развивающимися во время беременности. Имеющаяся на сегодняшний день информация свидетельствует о том, что мутации FVLeiden и FII G20210A могут быть связаны с рисками спонтанного аборта и повторных потерь плода.

In the 1990s, two gene polymorphisms — factor V Leiden (FVLeiden) and prothrombin G20210A (FII G20210A) were recognized as a genetic substrate for the development of thrombophilia. Polymorphism FVLeiden is associated with the development of resistance to anticoagulant action of protein  C, and polymorphism FII G20210A with a high level of prothrombin in plasma. In healthy individuals of Caucasian origin, the prevalence of FVLeiden is between 2 and 10%. In patients with venous thromboembolism, the prevalence FVLeiden is about 20%. FII G20210A is found in 1—5% of the general Caucasian population and in 4—18% of patients with venous thromboembolism. These indicators depend on the selection of patients included in the analysis. The relationship between gene polymorphisms and the development of venous thromboembolism in women during pregnancy is discussed. The high risks of venous thromboembolism have been described for women with a homozygous FVLeiden mutation. The study of the activated protein  C (APC) and factor  V interaction has yielded valuable insights into how perturbations in this association lead to venous thromboembolism. It is now clear that APC exerts anticoagulant effects beyond inactivating factor  V by cleaving at R306 and R506, generating inactive FV. Mutation in FVLeiden abrogates this effect. In women with a heterozygous FVLeiden or heterozygous FII G20210A, the risks of venous thromboembolism are significantly low. Regardless of genetic polymorphism, a positive family history of venous thrombosis increases the risk of developing venous thromboembolism during pregnancy. The relationship between genetic polymorphism and nonthrombotic complications developing during pregnancy is discussed. Mutations of FVLeiden and FII G20210A may be associated with the risks of spontaneous abortion and repeated fetal loss.

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The authors declare that there are no conflicts of interest present.