Abstract
Abstract Background: Hepcidin, a 25 amino acid peptide expressed in the liver, has been shown to have a major role in iron metabolism controlling iron release from reticuloendothelial and intestinal epithelial cells. Studies reported a potential role of iron loading modi- fier (Hepcidin) in poly-transfused beta-thalassemic patients for the -582 A>G polymorphic change (rs10421768)2 in the 5' flanking region of the HAMP (Hepcidin AntiMicrobial Peptide) gene encoding hepcidin. Objective: In this study we studied the genetic variant in the hepcidin gene (HAMP) promotor (C.-582 A>G) and the associations between this variant and iron overload in patients with B-thalassemia major. Subjects: Two groups were included in this study: Group I: included fifty one children with B-thalassemia major diagnosed by clinical signs, complete blood picture and Hemoglobin electrophoresis Nearly all children in group I were receiving regular red cell transfu- sion and regular oral iron chelation therapy (Deferasirox)and were clinically followed up in the hematology clinics of Alexandria University Children'sHospital(AUCH) and Damnhour Teaching Hospital. Group II: included twenty-two healthy children of matching age and sex with the previous group as controls. Methods: All patients included in the study were subjected to thorough history taking with special emphasis on : age at starting transfusion therapy, frequency of packed red cells transfusion, adherence to chelation by oral chelator (deferasirox), thorough clini- cal examination with special emphasis on: thalassemic features, hepatic and splenic size, cardiac examination, laboratory investi- gations including: routine investigations to diagnose B- thalassemia i.e, complete blood count, Haemoglobin electrophoresis, liver function tests: Alanine transaminase (ALT) and Aspartate transaminase (AST), kidney function tests: 3300d urea nitrogen (BUN) and Serum creatinine, c -reactive protein (CRP), iron 7rofile {serum iron,total iron binding capacity (TIBC) and serum ferritin (SF)} by ELISA, Genomic DNA was extracted from EDTA whole 7 lood samples using QIAamp DNA blood mini kit 50.C_582A>G (rs 10421768) SNP was detected by 5' nuclease allele discrimination assay using real-time PCR. Results: The mean serum ferritin was not significantly higher in patients with genotype AG/GG than patients with genotype AA (mean ± SD 2049.23 ± 848.27and 1081.67 ± 120.03 respectively ng/ml), Conclusion: The c.-582A > G HAMP promoter variant is associated with high serum iron and ferritin levels but with no significant difference between genotypes AG/GG and AA in patients with ẞ-thalassemia major. Keywords: ẞ-Thalassemia major (TM); DNA; EDTA