POPULATION-BASED STATISTICAL REVIEW OF ANTITHROMBIN III (SERPINC1) GENE MUTATIONS IN UZBEKISTAN

Abstract

Venous thromboembolic complications (VTECs), including deep vein thrombosis and pulmonary embolism, remain one of the leading causes of death and disability worldwide. In Central Asian countries, including Uzbekistan, the problem of thrombotic events is complicated by the insufficient availability of molecular genetic diagnostics and limited awareness of congenital forms of thrombophilia, among which antithrombin III deficiency occupies one of the key places. Antithrombin III is a glycoprotein synthesized in the liver and plays a central role in the formation of the body's anticoagulant defense. The gene encoding this protein (SERPINC1) is located on chromosome 1q25.1 and consists of 7 exons. Mutations SERPINC1 lead to the development of a qualitative or quantitative deficiency of antithrombin III, which, in turn, increases the risk of thrombosis by 5-50 times compared to the general population. More than 250 variants of mutations of SERPINC1 have been described in foreign literature, but there is practically no data for the countries of Central Asia. Meanwhile, Uzbekistan is characterized by a pronounced ethnogenetic mosaic, historical migration of peoples and a high proportion of consanguineous marriages in some regions. All these factors can significantly affect the prevalence of hereditary thrombophilias and determine a unique regional spectrum of mutations. At present, genetic diagnosis in Uzbekistan is largely limited to the study of FVL (G1691A) and prothrombin (G20210A) mutations, while SERPINC1, which is one of the most significant genes for thrombophilia, has not been sufficiently studied. This leads to frequent diagnostic skips, especially in young patients with early, recurrent, or familial episodes of thrombosis. In this regard, population-genetic analysis is SERPINC1 of strategic importance for the formation of national recommendations, the assessment of the real burden of congenital thrombophilias and the development of programs for personalized prevention of VTEC in Uzbekistan.