ВЛИЯНИЕ ГЕНА ФАКТОРА, ИНДУЦИРУЕМОГО ГИПОКСИЕЙ, НА ТЕЧЕНИЕ АНТРАЦИКЛИН-ИНДУЦИРОВАННОЙ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ

Abstract

Relevance. Chronic heart failure (CHF) is a serious complication in the treatment of tumor diseases due to the cardiotoxic effect of anticancer drugs, especially anthracyclines. Despite an ever-increasing understanding of the molecular basis of anthracycline-induced cardiotoxicity, the precise mechanisms of action remain unknown, limiting the ability to effectively prevent this complication of polychemotherapy (PCT). Aim. To evaluate the effect of polymorphism (rs11549465) of the hypoxia-inducible factor subunit 1 alpha (HIF1α) gene on the course of anthracycline-induced CHF. Materials and methods. The study included 114 women with CHF that developed 12 months after the end of breast cancer chemotherapy using anthracycline drugs. All patients received therapy with carvedilol and enalapril. The control group (n = 70) consisted of women who received doxorubicin as part of chemotherapy, but they did not develop CHF 12 months after completion of PCT. The HIF1α gene polymorphism (rs11549465) was assessed using polymerase chain reaction. The course of CHF was monitored at baseline, after 12 and 24 months. Results. No significant differences were found in the frequencies of the studied polymorphism of the HIF1α gene in the groups of patients with CHF and the control group. Consequently, HIF1α gene polymorphisms are not associated with an increased risk of developing cardiac dysfunction after tumor therapy with anthracycline antibiotics. However, it was found that in women with progression of CHF after chemotherapy with anthracyclines, the frequency of occurrence of the CT genotype was statistically significantly higher than that in the group of women without progression of this pathology after 24 months of prospective observation (68.5 and 23.3%, respectively, p = 0.009). Consequently, the presence of the CT genotype of the HIF1α gene (rs11549465) (OR = 2.93; p = 0.009) is associated with an unfavorable course of CHF after anthracycline chemotherapy. Conclusion. The results obtained may indicate a genetically determined predisposition to the progression of anthracycline-induced CHF. The presence of the CT genotype of the HIF1α gene (rs11549465) is associated with an unfavorable course of CHF after anthracycline chemotherapy, which can be realized through changes in the activity of HIF1α and, accordingly, the sensitivity of cardiomyocytes to hypoxia.