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:

• α-Globin gene deletion
• β-thalassemia (β-thal)
• β⁰/β⁺ genotype
• clinical severity
• hemoglobinopathy

Acknowledgements

The authors would like to thank the principal of Burdwan Medical College and Hospital, Burdwan, West Bengal and the director of the Institute of Child Health, Kolkata, West Bengal for providing support to this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The present study was supported by the Department of Biotechnology, Ministry of Science and Technology, India [No-BT/PR26461/MED/12/821/2018]. This study was also supported by the Department of Science and Technology, Government of West Bengal [Sanc. No-687(Sanc.)/ST/P/S&T/1G-20/2014].