Role of XmnI polymorphism in HbF induction in HbE/β and β-thalassaemia patients

  • Kaiissar Mannoor Institute for Developing Science and Health initiatives, Mohakhali, Dhaka-1212 http://orcid.org/0000-0002-2394-0447
  • Mohabbat Hossain Laboratory of Genetics and Genomics, Institute for developing Science and Health initiatives, Mohakhali, Dhaka-1212
  • Farjana Akther Noor Laboratory of Genetics and Genomics, Institute for developing Science and Health initiatives, Mohakhali, Dhaka-1212 and Department of Biochemistry and Molecular Biology, University of Dhaka-1000, Bangladesh
  • Golam Sarwer Bhuyan Infectious Disease Laboratory, Institute for Developing Science and Health initiatives, Mohakhali, Dhaka-1212, Bangladesh
  • Syeed Saleheen Qadri Laboratory of Genetics and Genomics, Institute for developing science and Health initiatives, Mohakhali, Dhaka-1212, Bangadesh
Keywords: β-thalassaemia, HbE/β-thalassaemia, XmnI-Gγ polymorphism, Hydroxyurea

Abstract

Background: Thalassaemia is one of the most common genetic blood disorders worldwide. Patients with β-thalassaemia major and HbE/β-thalassaemia are blood transfusion dependent. Foetal haemoglobin or HbF can play a role in disease manifestations in these patients and there is evidence that a homozygous state for XmnI polymorphic site, associated with increased expression of Gγ-gene, may play an important role among other factors in ameliorating the clinical severity of homozygous β-thalassaemia and thalassaemia intermedia. The aim of this review was to provide a comprehensive review of the role of XmnI polymorphic site for increased HbF production in HbE/β and β-thalassaemia patients.

Methods: Published literatures were reviewed on the allelic frequency of Xmn1 polymorphism and its effect on HbF induction among thalassaemia patients of different countries.

Results: In all β-thalassaemias, Hb F levels are relatively increased due to the selective survival of the erythroid precursors that synthesize relatively more γ-chains. The expression of HbF level is dominated by three different loci: HBG2: γ -158C>T, BCL11A, and HBS1L-MYB intergenic region. Genetic determinants influencing Hb F response can be within the β-globin complex or trans-acting. The published literature showed that the C>T substitution (rs7482144) at position –158 of the Gγ-globin gene, referred to as the XmnI-Gγ polymorphism, is a common sequence variant in all population groups, present at a frequency of 0.32 to 0.35. It was found in some studies, response to Hydroxyurea (HU) has been shown to be largely associated with the presence of the C>T polymorphism at -158 XmnI site (HBG2:c.- 53-158C>T) upstream of the Gγ-globin gene and HU therapy exerts a 2- to 9- fold increase in γ-mRNA expression in β-thalassaemia patients.

Conclusion: A number of various study groups around the world suggests that XmnI polymorphism is an important key regulator of disease severity of HbE/β and β-thalassaemia patients.

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Published
2019-12-30
How to Cite
Mannoor, K., Hossain, M., Noor, F., Bhuyan, G., & Qadri, S. (2019). Role of XmnI polymorphism in HbF induction in HbE/β and β-thalassaemia patients. Bangladesh Medical Research Council Bulletin, 45(3), 133-142. https://doi.org/10.3329/bmrcb.v45i3.44642
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Review Paper