Beta-Globin (HBB) Mutations and Catalase Gene Polymorphisms in Beta-Thalassemia Major Patients in Al-Diwaniyah, Iraq.

Background/Objectives: β-thalassemia major is a common inherited hemoglobin disorder caused by Hemoglobin Subunit Beta (HBB) mutations and often complicated by iron overload and oxidative stress. This study characterized the clinical, hematological, biochemical, and molecular profile of β-thalassemia major in Al-Diwaniyah, Iraq, focusing on HBB mutations and CAT promoter polymorphisms as oxidative modifiers. Methods: A retrospective case-control study included 100 transfusion-dependent patients and 50 healthy controls. Sociodemographic data, complete blood count, ferritin, lipid profile, catalase (CAT), and malondialdehyde (MDA) were assessed. HBB mutations, namely IVSI-1 (G>A), IVSI-6 (T>C), and CD39 (C>T), and CAT polymorphisms, namely rs1001179 (C>T) and rs7943316 (A>T), were genotyped. Results: Patients had high rates of family history (80%), consanguinity (80%), rural residence (74%), low education (60.6%), and poor socioeconomic status (71.4%). Compared with controls, they showed lower RBC, HGB, HCT, HDL, LDL, and CAT but higher ferritin, triglycerides, and MDA (all p < 0.001). Overall, 69% of patients carried at least one studied HBB mutations, while 31% remained uncharacterized. Mutant allele frequencies were 29% for IVSI-1 (A) and 25.5% each for IVSI-6 (C) and CD39 (T). The CAT polymorphism rs1001179 (C>T) was associated with disease risk (CT: 33% vs. 14%; OR = 3.25, p = 0.019), whereas rs7943316 (A>T) was not. IVS-I-1 (G>A)/CD39 (C>T) β0 mutations were associated with lower CAT activity (β = -0.205; p = 0.046). Conclusions: β-thalassemia in Al-Diwaniyah, Iraq, shows substantial clinical, genetic, and oxidative heterogeneity. Integrated HBB-CAT analysis may improve molecular diagnosis, risk stratification, and preventive strategies in high-consanguinity populations.