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Abstract Thalassemia is among the most common monogenic disorders in humans. It is prevalent in the Mediterranean region and the Middle East. Regular blood transfusion therapy and intestinal iron absorption lead to iron overload, with increased risk for related complications in the development and function of multiple vital physiological systems and organs in children with thalassemia. Iron overload can result in progressive organ damage grouped together under a condition called haemosiderosis. Important complications include growth retardation and delay of sexual maturation in children, and later involvement of the heart, liver, and endocrine system. The maintenance of normal iron levels is critical and is mainly succeeded by regulating intestinal absorption and by continuously recycling and reusing cellular iron due to the absence of an effective excretory mechanism for iron. HFE protein plays the role in the regulation of intestinal iron absorption and deposition in the tissues. A mutation in the HFE gene was identified as the cause for around 65% of the cases of classic hemochromatosis in Mediterranean region. The aim of this study to investigate HFE gene mutations (C282Y) and its possible association with Iron overload in children with Beta-thalassemia. This study included 76 children with β-thalassemia (41 boys and 35 girls) who were selected from the attendants of the Pediatric Hematology Clinic, Menoufia University Hospital with a mean age of 7.55± 4.24 years. They were on regular packed red cell transfusion. Children with abnormal thyroid functions, abnormal renal functions, diabetes mellitus and serological evidence of hepatitis B or C were excluded from the study. Fifty one (29 boys and 22 girls), age and sex matched healthy children were involved as a control group with a mean age of 8.31 ± 4.19 years. Included patients were subjected to detailed history and thorough clinical examination with special emphasis on history of splenectomy, frequency of blood transfusion and chelation therapy. All children subjected to full history taking, complete clinical examination. Renal and hepatic functions, Iron, ferritin and transferrin levels were measured. Complete blood picture were done. HFE gene mutations (C282Y) rs1800562 were assayed by SNP real time PCR. Our study showed that there wasa significantly increased frequency of the A genotype and A allele of rs1800562 SNP of HFE gene (C282Y) mutation in children with beta thalassemia compared to controls. There was a significant increase of serum Iron and ferritin levels in AA genotype than both AG and GG genotypes. Also, there was significant increase in splenectomy percent among AA genotype than other two genotypes in patients group. There was a significant increase number and % of patients with ferritin level equal or more than 2500 ng/ml as index of iron overload with AA and AG genotypes. There was a significant decrease of hepcidin levels in AA genotype than both AG and GG genotypes. Finally, frequency HFE C282Y mutation may relate to genetic susceptibility to beta thalassemia and correlated positively with decrease hepcidin levels and increase ferritin level as index of iron overload. |