Correlation of Iron Metabolism Genes Haplotypes with Beta Thalassemia Major patients in Palestineرسالة ماجستير

Abstract

Thalassemia are a group of common inherited blood disorders caused by defect in the globin protein production. Iron overload is associated with increase morbidity in transfusion - dependent thalassemia. we hypothesized that iron dysregulation may play a significant role in thalassemia pathogenesis. The aim of this study was to investigate the association of a number of single nucleotide polymorphisms (SNPs) in selected genes involved in Fe metabolism including rs11915082 I transferrin receptor 1 (TFRC) gene, rs1048230 and rs224589 in solute carrier family 11 member 2 (SLC11A2) gene, rs1439816 in solute carrier family 40 member 1 (SLC40A1) gene, rs10421768 and rs104894696 in hepcidin antimicrobial peptide (HAMP) gene and rs1799945 in the human homeostatic iron regulatory protein (HFE) with thalassemia and the corresponding iron overload complication in these patients. The study subjects comprised of 88 β-thalassemia patients and 88 controls. Genotypes were determined by RFLP-PCR, ARMS and Sanger’s sequencing. The results showed the C allele of rs1439816 in the ferroportin gene was associated with thalassemia pathogenesis (p < 0.0001, OR = 12.21, 95% IC =7.38- 20.22). However, genetic variants in the other indicated genes failed to show significant association with iron overload or other disease complications due to the sporadic treatment plans for most patients and absence of reliable medical records concerning regular follow up and accurate monitoring. The rs1439816 variant (specifically the C allele) in the ferroportin gene represents a fairly strong indicator in thalassemia patients which provides a reliable additional marker for the clinical complexity of the disease.