ANTIOXIDANT DEFENSE GENE POLYMORPHISMS AS MOLECULAR GENETIC PREDICTORS OF CARDIOTOXICITY IN PATIENTS WITH ACUTE LEUKEMIA

Abstract

Background: Cardiotoxicity remains one of the most important non-hematological complications in patients with acute leukemia receiving anticancer therapy. Oxidative stress plays a central role in myocardial injury, whereas genetic variations in antioxidant defense pathways may influence individual susceptibility to cardiovascular complications. Objective: To evaluate the association of SOD2 C14510A, GPX4 C718T, and CAT G262A polymorphisms with cardiotoxicity and cardiovascular complications in patients with acute leukemia. Methods: A retrospective observational study included 102 patients with acute leukemia and 97 age- and sex-matched healthy controls. Patients underwent clinical examination, electrocardiography, echocardiography, and assessment of cardiac biomarkers, including troponins and NT-proBNP. Genotyping of SOD2 C14510A, GPX4 C718T, and CAT G262A polymorphisms was performed using real-time polymerase chain reaction. Associations between genetic variants and cardiovascular complications were evaluated using odds ratios (ORs) with 95% confidence intervals (CIs). Results: The frequency of the SOD2 A allele was significantly higher in patients with acute leukemia than in healthy controls (34.31% vs. 21.65%; OR=1.90, 95% CI 1.21–2.95; p=0.01). The GPX4 T allele was more prevalent among patients with cardiovascular complications than among those without complications (50.78% vs. 38.16%; OR=1.67, 95% CI 0.92–3.03). Carriers of the CAT A allele demonstrated a tendency toward increased cardiotoxicity risk (OR=2.05), although statistical significance was not achieved. Unfavorable antioxidant gene variants were associated with elevated NT-proBNP and cardiac troponin levels, as well as reduced left ventricular ejection fraction. Conclusions: Genetic polymorphisms involved in antioxidant defense contribute to the development of cardiovascular complications in acute leukemia. The SOD2 C14510A polymorphism demonstrated the strongest association with cardiotoxicity and may serve as a promising molecular genetic marker for cardiovascular risk stratification. Comprehensive assessment of SOD2, GPX4, and CAT variants may improve personalized monitoring and prevention strategies in cardio-hematology.