α- and β-Globin Gene Mutations in Individuals with Hemoglobinopathies in the Chattogram and Sylhet Regions of Bangladesh

Abstract

Hemoglobinopathies, including α- and β-thalassemias and sickle cell disease, are among the most widely disseminated hereditary blood disorders worldwide. Bangladesh is considered a hotspot for hemoglobinopathies, and these diseases cause a significant health concern in the country. However, the country has a dearth of knowledge on the molecular etiology and carrier frequency of thalassemias, primarily due to a lack of diagnostic facilities, limited access to information, and the absence of efficient screening programs. This study sought to investigate the spectrum of mutations underlying hemoglobinopathies in Bangladesh. We developed a set of polymerase chain reaction (PCR)-based techniques to detect mutations in α- and β-globin genes. We recruited 63 index subjects with previously diagnosed thalassemia. Along with age- and sex-matched control subjects, we assessed several hematological and serum indices and genotyped them using our PCR-based methods. We identified that parental consanguinity was associated with the occurrence of these hemoglobinopathies. Our PCR-based genotyping assays identified 23 HBB genotypes, with the codons 41/42 (–TTCT) (HBB: c.126_129delCTTT) mutation leading the spectrum. We also observed the presence of cooccurring HBA conditions, of which the participants were not aware. All index participants in this study were on iron chelation therapies, yet we found they had very high serum ferritin (SF) levels, indicating inefficient management of the individuals undergoing such treatments. Overall, this study provides essential information on the hemoglobinopathy mutation spectrum in Bangladesh and highlights the need for nationwide screening programs and an integrated policy for diagnosing and managing individuals with hemoglobinopathies.

Keywords:

• α-Thalassemia (α-thal)
• β-thalassemia (β-thal)
• hemoglobin (Hb)
• polymerase chain reaction (PCR)
• sickle cell disease

Author contributions

Conceptualization: M.J. Hosen and S. Anwar; methodology: T. Kabir, S. Anwar and M.J. Hosen; software: T. Kabir and S. Anwar; investigation: T. Kabir, S. Anwar, J. Taslem Mourosi and S. Akter; validation and scrutinization: T. Kabir and S. Anwar; data curation: T. Kabir and S. Anwar; formal analysis: T. Kabir and S. Anwar; writing the original draft preparation: S. Anwar; writing, review and editing: S. Anwar; visualization: S. Anwar; supervision: M.J. Hosen; project administration: M.J. Hosen; funding acquisition: M.J. Hosen. All authors have read and agreed to the final version 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.

Data availability statement

All data collected and produced in this study that supports the conclusions of this article is included within the article.

Additional information

Funding

No specific grant was received for this study. S. Anwar was supported by the Maternal and Child Health (MatCH) program, Alberta Innovates, and the Women and Children’s Health Research Institutes in the forms of graduate scholarships. J. Taslem Mourosi received support from the COSMOS Scholars Program and the American Association of University Women (AAUW). M.J. Hosen was supported by the Shahjalal University of Science and Technology (SUST) Research Center (LS/2018/03/12), and the ICT Division of the People’s Republic of Bangladesh (Innovation Fund 2020-21 GO 207).