Frequency of human hemochromatosis (HFE) gene mutations in Egyptians with beta-thalassemia

Background Hereditary hemochromatosis is a disorder of iron metabolism characterized by increased iron intake and progressive storage and is related to mutations in the HFE gene. Two point mutations have been described and are referred to as H63D and C282Y. On the other hand, iron overload is a well-documented complication in thalassemia syndromes. Interactions between thalassemia and hemochromatosis may further increase iron overload. This work aimed at studying the frequency of the H63D and C282Y mutations of the HFE gene in an Egyptian population with beta-thalassemia (thalassemia major, intermedia, and minor) by comparing it with normal individuals without hemoglobinopathies. Participants and methods This study included 86 patients with beta-thalassemia; 40 of these patients had beta-thalassemia major and intermedia and the other 46 patients had beta-thalassemia minor (carriers). In addition, 70 individuals were included in the study and served as controls. All the populations studied were screened for H63D and C282Y mutations of the HFE gene using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. Results The allelic frequencies found for H63D and C282Y mutations in this study were 18.6 and 0%, respectively, among the total alleles of individuals with beta-thalassemia and 12.8 and 1.4% among controls without hemoglobinopathies. On comparing thalassemia cases, thalassemia carriers, and the control group, the allele frequency of the H63D mutation was significantly higher among beta-thalassemia carriers (24%) compared with patients with beta-thalassemia (12.5%) and controls (12.8%) (P = 0.049). Our study also found an almost significantly higher frequency of the heterozygote genotype for the H63D mutation in patients with beta-thalassemia (30.2%) than the controls (17.1%) (Fisher's test, P = 0.06). Compound heterozygosis for H63D and C282Y was found in one of the individuals in our control group. Conclusion The frequent occurrence of beta-thalassemia disease with the H63D gene mutation raises the possibility of genetic interactions and emphasizes the value of screening for HFE mutations in thalassemias to detect early cases of iron overload and to modify its treatment modalities. (C) 2013 The Egyptian Society of Haematology.