Genetic and Hematological Insights into β- Thalassemia Major: A Molecular and Clinical Investigation in Southern Iraq

Abstract

β-thalassemia major is a severe hemoglobin disorder caused by Hemoglobin Subunit Beta gene mutations, leading to impaired β-globin synthesis, chronic anemia, and transfusion dependency. This study aims to investigate the molecular and clinical aspects of β-thalassemia major in southern Iraq, focusing on HBB gene mutations, hematological alterations, and disease complications. A total of 100 participants 50 β-thalassemia major patients and 50 healthy with (28 males, 22 females) for both categories were analyzed. Genomic DNA extraction and PCR-sanger sequencing were conducted to detect single nucleotide polymorphisms (SNPs), while hematological and biochemical markers, including serum ferritin levels, were analyzed to assess disease severity and iron accumulation. A total of three SNPs were identified, with rs7480526 (71A>C) and rs1609812 (334G>A) showing a strong association with β-thalassemia susceptibility, whereas the rare (94-95insG) rs35238478 suggested a potential role in disease variation. Patients exhibited severe anemia, abnormal hemoglobin composition, and significantly elevated ferritin levels, particularly in those who had undergone splenectomy, emphasizing the urgent need for enhanced transfusion strategies and iron chelation therapy. Notable, consanguineous marriages and rural residence were recognized as key risk factors, highlighting the necessity of genetic counseling. These findings deepen our understanding of β-thalassemia major’s genetic and clinical landscape, underscoring the importance of early genetic screening, personalized disease management, and improved healthcare accessibility to mitigate disease burden.