Effect of Assorted Globin Haplotypes and α-Thalassemia on the Clinical Heterogeneity of Hb S-β-Thalassemia

Abstract

Hemoglobinopathies and thalassemias are the most commonly encountered monogenic disorders of blood in humans, posing a major genetic and public health problem round the globe. Hb S (HBB: c.20A>T)-β-thalassemia (β-thal) is a compound aberrant heterozygosity with inconsistent phenotypic expression, which are poorly described and clinically mapped. Comprehensive genetic characterization of such a population is highly warranted for complete understanding of the clinical heterogeneity, disease prognosis and therapeutic management. In this study, Hb S-β-thal (n = 60) patients, strictly defined by varying degrees of clinical presentations, were selected to evaluate their genotype-phenotype agreement. Furthermore, β-globin (n = 120) and α-globin gene clusters (n = 60) were genetically characterized and statistically correlated with clinical terminologies to explain the clinical heterogeneity. Our results revealed the association of the Arab-Indian haplotypes with nine different frameworks of β-thal together with the modulating role of α-thalassemia (α-thal). The study subjects, including carriers of β-thal haplotype III [– – – – – – –] (8.0%), presented with varying severe patterns of clinical symptoms such as painful crisis, multiple infections and splenomegaly, as an outcome of significantly less Hb F and higher Hb S levels (p < 0.5). The study findings indicated that together with α-thal, β-thal haplotypes and Hb F levels, may possibly provide a close justification to support the clinical heterogeneity in the study population.

Keywords:

• α-Thalassemia (α-thal)
• β-Thalassemia (β-thal) haplotype analysis
• Hb F
• IVS-I-5 (G>C) (HBB: c.95 + 5G>C)
• mutation
• Hb S (HBB: c.20A>T)- β-thal

Acknowledgments

The authors sincerely thank all the patients whose participation helped to make the research successful. As a gesture of gratitude to the late Dr. Dilip K. Patel (fund recipient, VIMSAR from the Department of Biotechnology, Government of India), the authors dedicate this study to his memory. Dr. Patel was a distinguished physician and a pioneer researcher, and his contribution to the field of abnormal hemoglobinopathies and thalassemias in western Odisha, India will be forever remembered. We are also grateful to Professor Mrs. Surinder Kaur Makhija, Ex-Professor in Biochemistry, Saraswati Bhuvan College, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India, for her valuable help in proofreading of the manuscript. P.M. Dash designed the study, conducted the experiments, analyzed the data and prepared the manuscript; P.K. Sahu analyzed data, interpreted the study results and edited the manuscript; S. Patel helped in collection of clinical data and cared for the patients; R.S. Mashon helped in collection of data and DNA isolation; K.R. Kharat and M.B. Mukherjee helped in the preparation of the manuscript.

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

This research was partly supported by funds from the Department of Biotechnology, Government of India.