Assessment of FOXO3 Gene Polymorphism in β Thalassemia Major and its Complications

Objectives: To assess the role of FOXO3 gene polymorphism (rs3800231) in β- thalassemia major (β-TM) and its complications in children. Background: Beta thalassemia is an inheritable condition that causes reduced hemoglobin synthesis, resulting in persistent anemia and complications in different organs. The forkhead box 3 (FOXO3) gene expresses a protein that is essential to several biological processes, such as erythroblast maturation. Methods: This study enrolled 150 children divided into three groups, 50 β-TM patients without complications, 50 β-TM patients with complications divided into cardiac complications and osteoporosis, and 50 age and gender-matched healthy children as controls. Analysis of FOXO3 gene polymorphism (rs3800231) by TaqMan allelic discrimination polymerase chain reaction. Quantitative estimation of hemoglobin fractions was done by hemoglobin electrophoresis, assessment of cardiac complications by echocardiography and osteoporosis by bone scan. Results: The GG genotype was more frequent among β-TM without complications and β-TM patients with complications than controls (p=0.01, 0.001 respectively), with no significant difference between both patient groups, and carried risk for β-TM with odds ratio (OR) of 5.115 (95% CI: 1.62–16.14) and risk for β-TM complications with OR of 8.48 (95% CI: 2.60-27.66). The G allele was more frequent among the β-TM without complications and β-TM with complications than controls. The frequency of regular blood transfusion, body mass index (BMI), serum ferritin, platelets, Hb F% and Hb A2% were considered risk factors for thalassemia complications. Conclusion: The GG genotype and G allele of rs3800231 polymorphism of the FOXO3 gene promote the susceptibility for the development of β-thalassemia major.