Two β-globin cluster-linked polymorphic loci in thalassemia patients of variable levels of fetal hemoglobin

Objective: To correlate different polymorphisms of the β-globin cluster with fetal hemoglobin (HbF) level in β-thalassemia and E-β thalassemia patients. Methods: Fifteen thalassemia patients, seven with high HbF and not requiring transfusion, eight with lower HbF and requiring transfusion were studied for β-globin mutation, concurrent inheritance of α-thalassemia, RFLP haplotype, a C → T polymorphism at -158 of Gγ and configuration of an (AT)_xT_y motif at -540 of β-globin gene. Results: Senegal 5'β-haplotype and the polymorphism at -158 of G_γ was (P = 0.063) was linked to the high-HbF phenotype but the (AT)₉T₅ configuration of the (AT) _xT_x motif was not (P = 0.6). Study of 30 chromosomes revealed 7 different configurations of the (AT)_xT_x motif. Association of these motifs with specific β-globin mutations of this region has also been determined. Conclusion: The Senegal haplotype and the polymorphism at -158 of G_γ was linked to the high-HbF phenotype.