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Genetic determinants related to pharmacological induction of foetal haemoglobin in transfusion-dependent HbE-β thalassaemia

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Abstract

Thalassaemia are the most common inherited autosomal recessive single gene disorders characterized by chronic hereditary haemolytic anaemia due to the absence or reduced synthesis of one or more of the globin chains. Haemoglobin E-β thalassaemia is the genotype responsible for approximately one half of all severe beta-thalassaemia worldwide. This study proposes to evaluate the effect of various molecular parameters on the response of hydroxyurea. Hydroxyurea was started at an initial dose of 10 mg/kg of body weight/day on 110 transfusion-dependent HbE-β thalassaemia patients. HbF level was measured by HPLC analysis. β-Thalassaemia mutations, XmnI and five other SNPs, and α-globin gene deletions and triplications were detected by ARMS-PCR, RFLP-PCR and Gap-PCR, respectively. Based on the factors for evaluating hydroxyurea-response, 42 patients were responders as they showed an increment of Hb from a mean baseline value of 6.45 g/dl (± 0.70) to 7.78 g/dl (± 0.72) post-therapy. Based on increase in HbF above the median value (14.72%) post-therapy, 78 patients were found to be responders. All the 78 responders showed mean decrease in transfusion of 74.26% (± 8.32) with a maximum decrease of 98.43%. There was a significant correlation between decrease in transfusion and increase in HbF level for all 78 responders. XmnI polymorphism showed the strongest association (p < 0.0001) with increase in HbF levels and Hb levels. Patients with α-globin gene deletions were better responders. It was concluded that hydroxyurea treatment is effective in transfusion-dependent HbE-β thalassaemia patients and the response is best in patients having both XmnI polymorphism and α-deletion.

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Acknowledgments

The authors would like to thank all the patients attending OPD, Thalassaemia Clinic and Day Care of IHTM, Medical College, Kolkata. They also thank all the laboratory technical staff who assisted with the research work.

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Authors and Affiliations

  1. Medical College, Institute of Haematology and Transfusion Medicine, 88, College Street, Kolkata, 700073, India

    Sujana Biswas, Arijit Nag, Rudra Ray & Maitreyee Bhattacharyya

  2. National Institute of Immunohaematology (ICMR), Mumbai, India

    Kanjaksha Ghosh

  3. Medical College, Kolkata, India

    Kaushik Roy & Anish Bandyopadhyay

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  1. Sujana Biswas
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  2. Arijit Nag
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Correspondence to Maitreyee Bhattacharyya.

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Biswas, S., Nag, A., Ghosh, K. et al. Genetic determinants related to pharmacological induction of foetal haemoglobin in transfusion-dependent HbE-β thalassaemia. Ann Hematol 98, 289–299 (2019). https://doi.org/10.1007/s00277-018-3536-x

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