Impact of Genotype of Beta Globin Gene on Hepatic and Myocardial Iron Content in Egyptian Patients with Beta Thalassemia

Abstract

Iron overload causes most of the mortality and morbidity associated with thalassemia. Excess iron deposits primarily in the liver, but once a threshold level is reached, iron loading may occur in other tissues such as the heart. Magnetic resonance imaging is a well established technique to noninvasively quantify myocardial and liver iron content. More than 300 disease-causing mutations have been identified. We aimed to determine the impact of genotype on liver iron content in patients with beta thalassemia. Cross sectional study was carried on 73 patients with beta thalassemia. MRI liver and heart was performed to determine hepatic and myocardial iron overload. Genotyping was determined by DNA sequencing technique. The mean liver iron content was 17.4 mg/g dw and mean cardiac T2* was 25.5 ms in our patients. Patients with b 0 b 0 were associated with significantly higher liver and myocardial iron content compared to those with b 0 b ? and b ? b ? genotypes. There was a clear association between genotype and both hepatic and myocardial iron overload. Patients with b 0 b 0 had significantly higher liver and heart iron content compared to those with b 0 b ? and b ? b ? genotypes. Liver iron content was strongly correlated to serum ferritin levels and myocardial iron overload.

Link between Genotype and Multi-Organ Iron and Complications in Children with Transfusion-Dependent Thalassemia

“…In the present study, we evaluated the impact of an underlying genetic defect on the development of disease complications in children with TDT. To the best of our knowledge, few studies, involving mainly patients from a limited area of Egypt, have explored this issue [ 14 , 16 ]. The children represent an ideal study population, due to the absence of the “aging” effect, with age “per se” being a powerful risk factor for the development of several complications [ 45 , 46 ].…”

“…However, hepatic, cardiovascular and endocrine complications still occur [ 13 , 14 ]. The underlying genetic defect in thalassemia is an important factor in the development of these complications because the homozygous β0 genotype state demands more red cells consumption and a greater rate of iron overloading [ 15 , 16 ].…”

Role of Complement Regulatory Proteins (CD55, CD59, and CD35) on Red Blood Cells of <i>β</i>-Thalassaemia Patients

“…It is the most common genetic disorder worldwide and occurs in approximately 4.4 of every 10,000 live births. Three main clinical forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor [12].…”

Assessment of Molecular Changes of Transfusion Dependent Beta Thalassemia Children in El Minia Governorate and Their Correlations with Patients Clinical Outcomes

“…In contrary to our results, on a study was done on attendants to the hematology clinic of Abulrish hospital, Cairo University, Egypt, found that the most common mutation is IVS 1-110 (34%) & most common heterozygous mutations are IVS 1-110(G>A) & IVS 1-6(T>C) (3) In study conducted on patients attend pediatric hematology unit of Zagazig University Hospital revealed that IVS1-1, IVS1-110 and IVS1-6 were the commonest mutations (26.7%, 22.6% and 18.5% respectively) (4) In study was conducted on Egyptian patients with β-thalassemia who were being treated in the Departments of Human Genetics and Hematology, Medical Research Institute, University of Alexandria, Egypt , stated that ten 150 Assessment of Molecular Changes of Transfusion Dependent Beta Thalassemia Children in El Minya different mutations were detected, the most frequent of which were IVS 1.6 [T>C] and IVS I.110 (G>A). These 2 common mutations accounted for 50% of the total tested chromosomes.…”