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Abstract β-thalassemia is a monogenic disorder usually caused by reduced or absent synthesis of the β-globin chain, one of the main components of adult hemoglobin. β-thalassemia is the most common chronic hemolytic anemia in Egypt, with a carrier rate of approximately 10%. The worldwide incidence rate is valued at one per 100,000. Blood transfusion is a traditional treatment for β-thalassemia that improves the patient’s anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands causing their dysfunctions as the iron regulatory system can’t excrete excess iron from the bloodstream. The FOXO3 transcription factors represent targets of the phosphatidylinositol 3-kinase/protein kinase B survival pathway controlling important biological processes, such as cell cycle progression, apoptosis, vascular remodeling, stress responses, and metabolism. This study aimed to assess the role of FOXO3 gene polymorphism rs3800231 in β-TM and its complications in children. The study included 150 subjects, divided into 3 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. All patients of this study were subjected to full history taking, clinical examination, routine investigations (complete blood count, Hb electrophoresis, serum ferritin, ECHO cardiography, bone density by Summary 86 DEXA scan), and specific laboratory testing (detection of FOXO3 gene polymorphism by Real-time PCR). Our results showed that: There was no significant difference in gender between patients and controls. However, the β-TM group with complications was significantly older than other groups. Weight, height, and BMI were significantly lower in β-TM patients than in controls. However, there was no considerable difference between β-TM patients with complications and β-TM patients without complications. β-TM patients with complications had a significantly higher rate of regular blood transfusion and higher incidence of splenectomy than β-TM patients without complications. The frequency of blood transfusion was significantly higher in β-TM patients with cardiac complications than in patients with osteoporosis. The Hb, MCV, and MCH were significantly lower in both β-TM patient groups than in controls. However, WBC count and PLT count were higher in the β-TM patient groups than in controls, with no considerable difference between β-TM patients with complications and β-TM patients without complications. Serum ferritin was higher in the β-TM patient groups than in controls. Also, it was higher in the β-TM patients with complications than β-TM patients without complications. However, there was no considerable difference between β-TM patients with cardiac complications and β-TM patients with osteoporosis. Summary 87 Hb F% was significantly higher in β-TM patients with complications than in β-TM patients without complications. However, Hb A2% was significantly higher in β-TM patients without complications than in β-TM patients with complications. In the current study, a significant difference was observed in the genotype frequency of the FOXO3 gene rs3800231 A/G SNP among the studied groups. The GG genotype was more frequent among the β-TM patients without complications and β- TM patients with complications than controls, with significant risk for β-TM where the OR was 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). However, there was no significant difference between β-TM patients with complications and β-TM patients without complications. Regarding genotype and allele distribution. AA genotype was more frequent among controls than patient groups. As regards allele distribution, the G allele was more frequent among the β- TM patients without complications and β-TM patients with complications than controls (p=0.003, <0.001 respectively), and carried a significant risk for thalassemia complications with an odds ratio of 3.622 (CI%: 1.20–6.58), meanwhile the A allele was more frequent in controls with no significant difference between the patients’ groups. The GG genotype was significantly more frequent in β-TM patients with cardiac complications than in β-TM patients without complications (p=0.044). Summary 88 Multivariate logistic regression analysis demonstrated that the frequency of regular blood transfusion, serum ferritin, platelets, Hb F%, and Hb A2% were considered risk factors for β-TM complications. There was a significant correlation between rs3800231 polymorphism and BMI in the non-complicated β-TM group. |