Study of Association of Hepcidin Promotor C-582 A>G Variant and Iron Over Load in B-Thalassemia Major

Nadia L Hatem¹, Maha Y Kamal¹, Doreen N Younan², Shimaa A Shaltout¹ and Ashraf M Ayad³*

¹Department of Pediatrics, Faculty of Medicine, Alexandria University, Egypt
²Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Egypt
³Pediatric Department - Damnhour Teaching Hospital, Egypt

*Shared Authorship: Ashraf M. Ayad , Pediatrics Department, Damnhour Teaching Hospital, Egypt.

Received: April 17, 2023; Published: June 03, 2023

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 modifier (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 transfusion and regular oral iron chelation therapy (Deferasirox)and were clinically followed up in the hematology clinics of Alexandria University Children's Hospital (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 clinical examination with special emphasis on: thalassemic features, hepatic and splenic size, cardiac examination, laboratory investigations 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

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Citation

Citation: Ashraf M. Ayad., et al. “Study of Association of Hepcidin Promotor C-582 A>G Variant and Iron Over Load in B-Thalassemia Major". Acta Scientific Paediatrics 6.7 (2023): 03-10.

Copyright

Copyright: © 2023 Ashraf M. Ayad., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.