الفهرس 
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Abstract
β-thalassemia major is a disease characterized by anemia and is associated with ineffective erythropoiesis and iron dysregulation resulting in iron overload. Iron overload is the major cause of late morbidity and mortality in transfusion dependent β-thalassemia patients. Major advances have been made in understanding iron availability for erythropoiesis and its dysregulation in β-thalassemia.
Hepcidin; which is considered as the ”master” iron regulatory hormone is produced by the liver, and it determines how much iron is absorbed from the diet and released from storage sites in the body. When the proteins involved in iron sensing and absorption are functioning properly, iron absorption is tightly regulated. The HFE protein interacts with other proteins on the cell surface to detect the amount of iron in the body. The HFE protein regulates the production of hepcidin.
The aim of the present study was to verify the influence of G71D of HAMP gene and H63D of HFE gene variants on iron overload in β-thalassemia major patients by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.
This study was performed on a total of 98 subjects. It included 52 patients with β-thalassemia major .They were 23 (44.2%) males and 29 (55.8%) females. Their age ranged between 2 and 25 years with a mean age of years 12 years. Forty -six age and sex matched healthy volunteers were included in the current study as a control group. They were 28 (60.9%) males and 18 (39.1%) females. Their age ranged between 2 and 13 years with a mean age of 6.31 years.
In the present study, iron profile in the form of) serum iron, serum TIBC, transferrin saturation and serum ferritin) was determined and genotyping of G71D of HAMP and of H63D of HFE variants was performed by PCR-RFLP technique using AciI and BclI restriction enzymes, respectively.
Genotyping of HAMP-G71D variant among the studied TM patients and controls revealed that heterozygous G71D mutation was detected in 13/52 (25%) and in 6/46 (13.0%) of the studied patients and controls, respectively. The incidence of G71D mutation of HAMP gene was higher in the studied patients than controls but statistical comparison showed no statistically significant difference (p=0.200). Borderline statistically significant difference in the incidence of heterozygous H63D mutation of HFE gene was found among the studied patients 12/52 )23.1%) in comparison to the control group 4/46 )8.7%) (p=0.062).
Borderline significance was observed between mean ferritin level (2636.35±1346.57 ng/mL) in patients received > 50 transfusions /life and patients received ≤ 50 transfusions/life (1915±758.54 ng/mL) (p=0.091).
In the current study, the identification of either HAMP- G71D or HFE-H63D mutation in TM patients did not determine which TM patients were at risk for heavy iron overload since patients with either HAMP-G71D or HFE-H63D variants did not show statistically significant difference in their iron overload parameters in relation to wild type patients.
No statistically significant difference was observed between patients heterozygous for the H63D mutation of the HFE gene or G71D of the HAMP gene and those with wild type among the regularly chelated or the irregularly chelated patients.
Multivariate regression analysis of independent factors that may significantly affect serum ferritin level was done and revealed that only the number of blood transfusions taken in life significantly increase serum ferritin level (p=0.003).