الفهرس 
T HALASSEMIAOnly 14 pages are availabe for public view
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Abstract
Abstract
Background: β-thalassemia major (β-TM) is an inherited blood disorder that requires liflong transfusion with inevitable iron overload leading to oxidant-antioxidant disturbance and endothelial dysfunction. Endothelin-1 (ET-1), a potent endogenous vasoconstrictor, causes fibrosis of the vascular cells and stimulates production of reactive oxygen species. Aim: To assess endothelin-1 gene polymorphism in pediatric patients with β-TM as a potential marker for vascular dysfunction and its possible relation to pulmonary and renal complications. Methods: Fifty-nine β-TM patients without symptomatic cardiac or renal disease were compared to 95 healthy controls and studied stressing on splenectomy, transfusion history, chelation therapy, markers of hemolysis and serum ferritin and urinary albumin-to-creatinine ratio (UACR) to detect micro- or macro-albuminuria. Endothelin-1 gene polymorphism (G8002A) was determined using polymerase chain reaction (PCR)‑restriction fragment length polymorphism method. Screening for pulmonary hypertension and cardiovascular abnormalities was performed by the non-invasive doppler echocardiograpghy. Results: Two alleles of of the endothelin-1 gene polymorphism (G8002A) were detected in the studied population; the A allele and G allele. Accordingly, three genotypes were identified; GG (150+208 bp), GA (358, 150 and 208 bp) and AA (358 bp). The AA genotype and allele A of the endothelin-1 gene polymorphism (G8002A) were significantly higher among β-TM patients than controls. β-TM patients with AA genotype showed that higher systolic and diastolic blood pressure and transfusion index as well as higher number of patients with cardiac disease, pulmonary hypertension risk or nephropathy compared with GG & GA genotypes. Hemoglobin level was significantly lower while LDH, serum ferritin were significantly higher in patients with AA genotype compared with GG & GA genotypes. Conclusion: Endothelin-1 gene polymorphism (G8002A) could be a possible genetic marker for prediction of increased susceptibility to cardiopulmonary and renal complications among pediatric patients with β-TM. It might play a significant role in disease severity or individual clinical outcomes.