Association between Different Polymorphic Markers and β-Thalassemia Intermedia in Central Iran

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Beta-thalassemia intermedia (β-TI) presents as moderate anemia and hepatosplenomegaly, often without transfusion dependence.
• Understanding the molecular basis of β-TI phenotypes is crucial for effective management and genetic counseling.
• Iranian patients exhibit a spectrum of β-TI severity, necessitating investigation into local genetic factors.

Purpose of the Study:

• To determine the molecular underpinnings of the clinical phenotype in Iranian β-TI patients.
• To investigate the association of specific β-globin gene mutations, α-globin gene deletions, and RFLP haplotypes with β-TI.
• To elucidate the role of the XmnI polymorphism in modulating β-TI severity.

Main Methods:

• Screening of 50 β-TI patients for three prevalent β-globin gene mutations (IVS-II-1, IVS-I-110, IVS-I-5).
• Analysis of α-globin gene deletions, XmnI polymorphisms, and RFLP haplotypes within the β-globin gene cluster.
• Statistical analysis to determine linkage and association between genetic factors and clinical phenotype.

Main Results:

• Fifty-eight percent of patients carried the screened β-globin gene mutations.
• The HBB: c.315+1G>A mutation was significantly linked to haplotype [+ - + +] (57.69%).
• Linkage disequilibrium between the XmnI polymorphism (NG_000007.3: g.42677C>T) and HBB: c.315+1G>A (80.76%) was associated with increased Hb F production, explaining milder phenotypes.

Conclusions:

• The genetic basis of mild β-TI in Iran is multifactorial, involving specific β-globin mutations and their interaction with regulatory elements.
• The coinheritance of the XmnI polymorphism with the HBB: c.315+1G>A mutation and haplotype [+ - + +] is a key factor in the mild phenotype of β-TI.
• These findings highlight the importance of comprehensive genetic screening for β-TI patients to predict disease severity and guide treatment strategies.