Effect of deletions in the α-globin gene on the phenotype severity of β-thalassemia

Abstract

Thalassemia is the most common inherited hemoglobinopathy worldwide. Variation of clinical symptoms in this hemoglobinopathy entails differences in disease-onset and transfusion requirements. The aim of this study was to investigate the role of α-globin gene deletions in modulating the clinical heterogeneity of β-thalassemia (β-thal) syndromes. A total number 270 β-thal subjects were enrolled. Hematological parameters were recorded. β-Globin mutations were determined by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR), gap-PCR and Sanger sequencing. α-Globin gene deletions were determined by multiplex PCR. Out of 270 β-thal subjects, 19 carried β⁺/β⁺, 74 had β⁰/β⁰ and 177 had the β⁰/β⁺ genotype. When we determined the severity of the different β-thal subjects in coinherited with the α gene deletion, it was revealed that, 84.2% β⁺/β⁺ subjects carried a non severe phenotype and did not have an α gene deletion. Of the β⁰/β⁰ individuals, 95.9% presented a severe phenotype, irrespective of α-globin gene deletions. In cases with the β⁰/β⁺ genotype, 19.2% subjects also carried a deletion on the α gene. Of these, 61.8% presented a non severe phenotype and 38.2% were severely affected. Only in the β⁰/β⁺ category did α gene deletions make a significant contribution (p < 0.001) toward alleviation of clinical severity. Therefore, it can be stated that α-globin gene deletions play a role in ameliorating the phenotype in patients with a β⁺/β⁰ genotype.

Keywords: clinical severity; hemoglobinopathy; α-Globin gene deletion; β-thalassemia (β-thal); β0/β+ genotype.