Gene polymorphisms role of blood coagulation in myocardial infarction development in patients with malignant tumors of thoracoabdominal localization

Aim. To evaluate the role of polymorphic variants of blood coagulation genes (F2, F5, F7, F13, FGB, ITGA2, ITGB3, PAI-1) in the development of myocardial infarction in patients with malignant tumors of thoracoabdominal localization.

Materials and methods. The study included 143 patients with thoracoabdominal tumors operated in the oncological Department of surgical methods of treatment No.11 (thoracic Oncology) of the thoracoabdominal Department of the Blokhin National Medical Research Center of Oncology in 2018–2019. The study group (n=62) consisted of patients with a history of myocardial infarction or in the perioperative period. The control group (n=81) included patients who did not have severe concomitant cardiovascular diseases, including a family history. Molecular genetic study to determine the gene polymorphisms of blood coagulation were performed in the laboratory of clinical oncogenetic of the Blokhin National Medical Research Center of Oncology with use of reagents “Cardiogenetic Thrombophilia” (LLC “DNA-Technology”, Russia, RU No. FSR 2010/08414 from 22.11.2016).

Results. In the study group, 90.3% (n=56) of cases showed polymorphism -675 5G>4G of the PAI-1 gene (SERPINE1, a plasminogen activator inhibitor) associated with a decrease in the activity of the fibrinolytic system and an increased risk of thrombosis. In the control group, this mutation was observed significantly less frequently – in 67.9% (n=55) of cases (p<0.001). In the group of patients with myocardial infarction, polymorphism 807 C>T of the ITGA2 (integrin a2) gene responsible for platelet aggregation was detected in 66.1% (n=41) compared to 19.8% (n=16) in the control group (p<0.0001). Polymorphism 1565 T>C of the ITGB3 gene (platelet-derived fibrinogen receptor) responsible for fibrinogen-induced platelet aggregation was observed in 25.8% (n=16) of cases in the group of patients with myocardial infarction and in 12.4% (n=10) of cases in the group of patients without concomitant severe cardiovascular pathology (p<0.05). In 48.4% (n=30) of patients of the study group, genetic disorders of the FGB gene (fibrinogen, missense mutation -455G>A) were also registered, which resulted in the development of dysfibrinogenemia, leading to increased blood thrombogenicity; in the control group, this mutation was 2 times less common – 25.9% (n=21) of cases (p<0.01). Polymorphism 1691 G>A of the F5 gene (coagulation factor V, Leiden factor), which is considered one of the most significant genetic risk factors for thrombosis in Caucasians, was detected in 4.8% (n=3) of cases in the study group, while this mutation was not found in the control group. Polymorphism 20210 G>A of the F2 gene (coagulation factor II prothrombin), which is a key protein of the coagulation cascade associated with increased blood levels of prothrombin, was observed in 3.2% (n=2) of patients after myocardial infarction; in the control group, the carrier of this polymorphism was not found in any case. Disorders in the genes that promote hypocoagulation were also noted. Among patients who had a myocardial infarction, polymorphism 10976 G>A of the F7 gene (coagulation factor VII) was detected in 17.7% (n=11) of cases, polymorphism 103 G>T of the F13 gene (coagulation factor XIII) – in 41.9% (n=26) of cases. In patients of the control group, these genetic aberrations were found: in 18.5% (n=15) of cases – a mutation in the F7 gene (p>0.05) and in 45.7% (n=37) – in the F13 gene (p>0.05), respectively.

Conclusion. Based on the results of a molecular genetic study of factors associated with thrombogenic risk, a statistically significant difference in the frequency of occurrence of polymorphisms of genes involved in the process of thrombosis (polymorphisms: -455 G>A of the FGB gene, 807 C>T of the ITGA2 gene, 1565 T>C of the ITGB3 gene, -675 5G>4G of the PAI-1 gene) in patients who had a myocardial infarction, compared with patients without severe concomitant cardiovascular diseases. The frequency of 1691 G>A polymorphism of the F5 gene, one of the most significant genetic risk factors for thrombosis, reached 4.8%. The obtained data on the use of molecular genetic markers of thrombophilia in patients with malignant tumors of thoracoabdominal localization allow us to identify a group of patients with a high risk of developing perioperative myocardial infarction and take additional measures for the prevention and treatment of thrombotic complications.