The impacts of beta globin gene mutations and Xmn IGγ polymorphism (HBG2 c. -211 C > T) on the clinical features of Hb Eβ-thalassemia patients in Bangladesh

Abstract Haemoglobin E β-thalassemia (Hb Eβ-thal), characterized by the presence of codon 26 (G > A), HBB :c.79G > A mutation with another pathogenic variant is a common blood disorder in South-Asia, especially in Bangladesh. The disorder can range from mild and asymptomatic anemia to life-threatening forms. Here, we performed molecular analysis to understand how mutations in the HBB gene and the XmnI polymorphism influence the severity and transfusion requirements in patients with Hb Eβ-thalassemia. This study found that individuals with the codon 16 (-C), HBB :c.51delC mutation required regular blood transfusions, whereas those with the codon 30 (G > C), HBB :c.92G > C mutation had the lowest transfusion dependency, at only 6.7%. Patients with codon 30 (G > C), HBB :c.92G > C mutation had the highest response to hydroxyurea therapy (76.7% ( n = 23)), while patients with codon 16 (-C), HBB :c.51delC mutations had the lowest response (0% ( n = 14)). The codon 16 (-C), HBB :c.51delC mutation was associated with the lowest mean HbF level (24.8%, SD = 7.7), whereas the codon 30 (G > C), HBB :c.92G > C mutation was associated with the highest mean HbF level (41.9%, SD = 16.10). Regarding XmnI polymorphism, codon 16 (-C), HBB :c.51delC mutation was associated with the highest wild type (-/-) ( n = 11) genotype, while codon 30 (G > C), HBB :c.92G > C mutation was associated with the highest homozygous mutated (+/+) ( n = 11) and the least wild type (-/-) ( n = 4) of XmnI polymorphism genotype. This study provides clinically relevant insights into treatment strategies involving HU therapy and the management of Hb Eβ-thalassemia patients with codon 30 (G > C), HBB :c.92G > C and codon 16 (-C), HBB :c.51delC mutations.