Alpha globin gene deletions in amelioration of clinical severity in beta haemoglobinopathy subjects with the β0/β+ genotype

Abstract

Thalassemia is the commonest inherited hemoglobinopathy worldwide. Variation of clinical symptoms entail differences in disease-onset and transfusion requirements. Our objective was to investigate the role of alpha gene deletions in modulating the clinical heterogeneity of thalassemia syndromes. A total of 214 individuals with diagnosed beta-thalassemia major/intermedia were included in the study. Beta globin mutations were determined and categorized as {beta}+ and {beta}0. Eight common alpha globin gene deletions were detected by multiplex GAP-PCR. Out of the 17 individuals with {beta}+/{beta}+, 16 did not harbour alpha deletions (/), and most of them were non-severe. On the other hand, out of 46 individuals with {beta}0/{beta}0, 30 did not reveal alpha deletions, whereas 16 possessed one or more alpha deletion(s). Accordingly, most of them presented as clinically severe. Out of the 151 {beta}0/{beta}+ individuals, 119 were negative for alpha deletion, whereas 32 possessed alpha deletions. It was observed that, only in this last category, alpha deletions made a significant contribution (P< 0.0001) in modulation of clinical non severity in this genotype. In conclusion, alpha globin gene deletions play a role to help in ameliorating the phenotype in the {beta}+/{beta}0 genotype. However, they may have only minor/no role in patients with {beta}+/{beta}+ or {beta}0/{beta}0 genotype.