Medical Science
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DOI: Combined Influence Of Sod2 And Edn1 Genetic Polymorphisms On Chemotherapy-Related Cardiotoxicity Risk In Acute Leukemia Patients
Kayumov A.A. , Republican Specialized Scientific and Practical Medical Center of Hematology, Uzbekistan, Tashkent State Medical University, Uzbekistan Zokirova M.B. , Tashkent State Medical University, UzbekistanAbstract
Background: Chemotherapy-related cardiotoxicity is a serious complication in acute leukemia patients, with significant interindividual variability suggesting a genetic component. Polymorphisms in genes regulating oxidative stress and vascular tone, such as SOD2 and EDN1, may influence individual susceptibility.
Objective: To evaluate the impact of SOD2 C14510A and EDN1 Lys197Asn polymorphisms, both individually and in combination, on the risk of cardiotoxic complications in acute leukemia patients undergoing chemotherapy.
Methods: A clinical-genetic study included 102 acute leukemia patients (64 with cardiotoxicity, 38 without) and 97 healthy controls. Cardiotoxicity was defined by clinical, biomarker, and echocardiographic criteria. Genotyping was performed using PCR. Statistical analysis included allele/genotype frequency comparison and odds ratio calculation.
Results: The SOD2 A allele (34.3% in patients vs. 22.0% in controls; *p*<0.05) and A/A genotype (15.6% in cardiotoxicity subgroup vs. 5.2% without) were more frequent in patients with complications. The EDN1 Asn allele was also more common in patients with cardiotoxicity (28.1% vs. 22.4%). While individual polymorphisms showed non-significant trends toward increased risk (e.g., SOD2 A/A OR=3.46, *p*>0.05), combined carriage of SOD2 A and EDN1 Asn alleles was associated with a significantly higher frequency of cardiotoxicity (OR=3.26, 95% CI: 0.87–12.19, *p*=0.04).
Conclusion: The SOD2 A allele and EDN1 Asn allele are associated with an increased risk of chemotherapy-induced cardiotoxicity in acute leukemia patients. Their combined presence suggests an additive effect, highlighting the role of genetic predisposition in cardiotoxicity and supporting the integration of genetic markers into personalized risk assessment strategies.
Keywords
Cardiotoxicity, Chemotherapy, Genetic Polymorphisms
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