Effect of deletions in the alpha-globin gene on the phenotype severity of beta-thalassemia

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 alpha-globin gene deletions in modulating the clinical heterogeneity of beta-thalassemia (beta-thal) syndromes. A total number 270 beta-thal subjects were enrolled. Hematological parameters were recorded. beta-Globin mutations were determined by amplified refractory mutation system-polymerase chain reaction (ARMS-PCR), gap-PCR and Sanger sequencing. alpha-Globin gene deletions were determined by multiplex PCR. Out of 270 beta-thal subjects, 19 carried beta(+)/beta(+), 74 had beta(0)/beta(0) and 177 had the beta(0)/beta(+) genotype. When we determined the severity of the different beta-thal subjects in coinherited with the alpha gene deletion, it was revealed that, 84.2% beta(+)/beta(+) subjects carried a non severe phenotype and did not have an alpha gene deletion. Of the beta(0)/beta(0) individuals, 95.9% presented a severe phenotype, irrespective of alpha-globin gene deletions. In cases with the beta(0)/beta(+) genotype, 19.2% subjects also carried a deletion on the alpha gene. Of these, 61.8% presented a non severe phenotype and 38.2% were severely affected. Only in the beta(0)/beta(+) category did alpha gene deletions make a significant contribution (p < 0.001) toward alleviation of clinical severity. Therefore, it can be stated that alpha-globin gene deletions play a role in ameliorating the phenotype in patients with a beta(+)/beta(0) genotype.