Abstract
BACKGROUND: Serum ferritin (SF) monitors secondary iron overload in beta-thalassemia (b-thalassemia). Transferrin (TRF) has been shown to reverse iron accumulation in experimental models, but its role in transfusion-dependent beta-thalassemia (TDT) patients remains unclear. This study aims to explore the relationship between TRF and SF in TDT patients and to reveal the unique connection between specific genotypes and iron metabolism, providing potential therapeutic targets for clinical practice. METHODS: This cross-sectional study includes 817 TDT patients (b0/b0 genotype: n=560; b0/b+ genotype: n=257). We use genotype-phenotype analysis and employ logistic regression and restricted cubic spline (RCS) curves to assess the association between TRF and SF. RESULTS: Significant differences were observed between the b0/b0 and b0/b+ genotypes in terms of age at first transfusion, transfusion requirements, chelation initiation age, reticulocyte count, red blood cell count, red cell distribution width-coefficient of variation (RDW-CV), fetal haemoglobin (HbF) level, splenomegaly, and SF. b0/b0 patients presented with more severe clinical phenotypes. SF was significantly associated with TRF, HbF, RDW-CV, and chelation therapy. RCS analysis revealed a dose-response relationship with a negative linear correlation between TRF and SF (OR=0.26, P<0.001), indicating that higher TRF levels are linked to lower SF risk. CONCLUSIONS: This study systematically confirms for the first time a significant negative correlation between high TRF levels and high SF risk in TDT patients. This new finding may help clinicians more effectively manage iron overload, especially in patients with different genotypes.