Title : Prognostic value of the C718T polymorphism in the GPX4 gene for cardiovascular complications in patients with acute leukemia
Abstract:
Background: Chemotherapy-induced cardiotoxicity is a major complication in patients with acute leukemia, often associated with oxidative stress. The glutathione peroxidase 4 (GPX4) gene play a critical role in antioxidant defense and cellular protection. This study evaluated the predictive value of the C718T polymorphism in the GPX4 gene for cardiovascular complications in leukemia patients undergoing chemotherapy.
Methods: A cohort of patients with acute leukemia was divided into subgroups: with and without cardiovascular complications, and compared to a healthy control group. Genotyping for GPX4 (C718T) was performed. Sensitivity (SE), specificity (SP), area under the ROC curve (AUC), odds ratios (OR), 95% confidence intervals (CI), and p-values were calculated for alleles (C, T) and genotypes (C/C, C/T, T/T) using logistic regression and ROC analysis.
Results: The T/T genotype was associated with a threefold increased risk of cardiovascular complications compared to patients without complications (OR=3.33; 95% CI: 1.08–10.29), although the p-value was not statistically significant (p=0.58). The T allele also showed a trend toward elevated cardiotoxicity risk (OR=1.67; CI: 0.94–2.97) in patients with complications. Sensitivity and specificity were modest across all genotypes (SE 0.22–0.62, SP 0.38–0.89), and AUC values did not exceed 0.59, indicating limited discriminatory power.
Conclusion: While the C718T polymorphism in the GPX4 gene demonstrates limited diagnostic performance, the T/T genotype may be a potential genetic risk factor for cardiotoxicity in patients with acute leukemia. Further studies with larger cohorts are needed to validate its prognostic utility.