Frequency of C282Y and H63D Mutations of HFE Gene and Their Correlation with Iron Status in Iranian Beta-Thalassemia Major Patients

Background: Co-inheritance of hemochromatosis (HFE) gene mutations may play an essential role in the pathogenesis of iron overload in beta-thalassemia major (BTM) patients. The present study aimed to investigate the prevalence of HFE C282Y and H63D mutations in BTM patients and their correlation with some demographic data and biochemical iron markers. Materials and Methods: The study population consisted of 65 BTM patients and 200 apparently healthy matched controls. The genotyping of HFE gene mutations were conducted by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. Plasma ferritin levels were determined by enzyme immunoassay. Plasma iron and transferrin levels were assessed by routine laboratory methods. Data analysis was performed using SPSS (version 22). Results: The carrier frequency of the H63D mutation was 20% with an allele prevalence of 12.31% in BTM patients, while in the control subjects these values were 21% and 11.75%, respectively (p>0.05 for both). The HFE C282Y gene mutation was not detected in BTM patients and only detected in the 1.5% of controls. The carriers of HFE H63D mutation had significantly higher plasma ferritin levels, iron levels and transferrin saturation levels than non-carriers (p=0.005, p=0.008, p=0.042, respectively). Moreover, no significant differences were observed regarding the mean volume of transfused blood and splenectomy rate between BTM patients with and without HFE H63D mutation. Conclusion: The present study demonstrated HFE H63D mutation as a significant contributing factor for iron overload in BTM patients. However, the genotype and allele distribution of HFE H63D and C282Y mutations didn’t differ significantly between the two groups.