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Epigenetic insights and potential modifiers as therapeutic targets in β–thalassemia
Zakaria, Nur Atikah Abdullah, Wan Zaidah Bahar, Rosnah Yusoff, Abdul Aziz Mohamed Wahab, Ridhwan Abdul Shamsuddin, Shaharum Johan, Muhammad Farid
Zakaria, Nur Atikah
Abdullah, Wan Zaidah
Bahar, Rosnah
Yusoff, Abdul Aziz Mohamed
Wahab, Ridhwan Abdul
Shamsuddin, Shaharum
Johan, Muhammad Farid
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Epub Date
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2021-05-18
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Abstract
Thalassemia, an inherited quantitative globin disorder, consists of two types, α– and β– thalassemia. β–thalassemia is a heterogeneous disease that can be asymptomatic, mild, or even severe. Considerable research has focused on investigating its underlying etiology. These studies found that DNA hypomethylation in the β–globin gene cluster is significantly related to fetal hemoglobin (HbF) elevation. Histone modification reactivates γ-globin gene expression in adults and increases β–globin expression. Down-regulation of γ–globin suppressor genes, i.e., BCL11A, KLF1, HBG-XMN1, HBS1L-MYB, and SOX6, elevates the HbF level. β–thalassemia severity is predictable through FLT1, ARG2, NOS2A, and MAP3K5 gene expression. NOS2A and MAP3K5 may predict the β–thalassemia patient’s response to hydroxyurea, a HbF-inducing drug. The transcription factors NRF2 and BACH1 work with antioxidant enzymes, i.e., PRDX1, PRDX2, TRX1, and SOD1, to protect erythrocytes from oxidative damage, thus increasing their lifespan. A single β–thalassemia-causing mutation can result in different phenotypes, and these are predictable by IGSF4 and LARP2 methylation as well as long non-coding RNA expression levels. Finally, the coinheritance of β–thalassemia with α–thalassemia ameliorates the β–thalassemia clinical presentation. In conclusion, the management of β–thalassemia is currently limited to genetic and epigenetic approaches, and numerous factors should be further explored in the future.
Citation
Zakaria NA, Islam MA, Abdullah WZ, Bahar R, Mohamed Yusoff AA, Abdul Wahab R, Shamsuddin S, Johan MF. Epigenetic Insights and Potential Modifiers as Therapeutic Targets in β–Thalassemia. Biomolecules. 2021; 11(5):755. https://doi.org/10.3390/biom11050755
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Research Unit
PubMed ID
34070036 (pubmed)
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Journal article
Language
en
Description
© 2021 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/biom11050755
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ISSN
2218-273X
EISSN
2218-273X
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This work was supported by Fundamental Research Grant Scheme (203/PPSP/6171214) to M.F.J. from the Ministry of Higher Education, Malaysia.
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Licence for published version: Creative Commons Attribution 4.0 International