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Genetic determinants related to pharmacological induction of foetal haemoglobin in transfusion-dependent HbE-β thalassaemia.
Ann Hematol 2019; 98(2):289-299AH

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.

Authors+Show Affiliations

Medical College, Institute of Haematology and Transfusion Medicine, 88, College Street, Kolkata, 700073, India.Medical College, Institute of Haematology and Transfusion Medicine, 88, College Street, Kolkata, 700073, India.National Institute of Immunohaematology (ICMR), Mumbai, India.Medical College, Institute of Haematology and Transfusion Medicine, 88, College Street, Kolkata, 700073, India.Medical College, Kolkata, India.Medical College, Kolkata, India.Medical College, Institute of Haematology and Transfusion Medicine, 88, College Street, Kolkata, 700073, India. mbhattyacharyya@yahoo.co.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30413899

Citation

Biswas, Sujana, et al. "Genetic Determinants Related to Pharmacological Induction of Foetal Haemoglobin in Transfusion-dependent HbE-β Thalassaemia." Annals of Hematology, vol. 98, no. 2, 2019, pp. 289-299.
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. 2019;98(2):289-299.
Biswas, S., Nag, A., Ghosh, K., Ray, R., Roy, K., Bandyopadhyay, A., & Bhattacharyya, M. (2019). Genetic determinants related to pharmacological induction of foetal haemoglobin in transfusion-dependent HbE-β thalassaemia. Annals of Hematology, 98(2), pp. 289-299. doi:10.1007/s00277-018-3536-x.
Biswas S, et al. Genetic Determinants Related to Pharmacological Induction of Foetal Haemoglobin in Transfusion-dependent HbE-β Thalassaemia. Ann Hematol. 2019;98(2):289-299. PubMed PMID: 30413899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genetic determinants related to pharmacological induction of foetal haemoglobin in transfusion-dependent HbE-β thalassaemia. AU - Biswas,Sujana, AU - Nag,Arijit, AU - Ghosh,Kanjaksha, AU - Ray,Rudra, AU - Roy,Kaushik, AU - Bandyopadhyay,Anish, AU - Bhattacharyya,Maitreyee, Y1 - 2018/11/09/ PY - 2018/03/14/received PY - 2018/10/23/accepted PY - 2018/11/11/pubmed PY - 2019/1/29/medline PY - 2018/11/11/entrez KW - Alpha-deletion KW - Foetal haemoglobin (HbF) KW - HbE-β thalassaemia KW - Hydroxyurea KW - Transfusion KW - Xmn1 polymorphism SP - 289 EP - 299 JF - Annals of hematology JO - Ann. Hematol. VL - 98 IS - 2 N2 - 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. SN - 1432-0584 UR - https://www.unboundmedicine.com/medline/citation/30413899/Genetic_determinants_related_to_pharmacological_induction_of_foetal_haemoglobin_in_transfusion_dependent_HbE_β_thalassaemia_ L2 - https://dx.doi.org/10.1007/s00277-018-3536-x DB - PRIME DP - Unbound Medicine ER -