Epigenetic insights and potential modifiers as therapeutic targets in β–thalassemia

Zakaria, Nur Atikah and Islam, Md Asiful and Abdullah, Wan Zaidah and Bahar, Rosnah and Mohamed Yusoff, Abdul Aziz and Abdul Wahab, Ridhwan and Shamsuddin, Shaharum and Johan, Muhammad Farid (2021) Epigenetic insights and potential modifiers as therapeutic targets in β–thalassemia. Biomolecules, 11 (5). pp. 1-20. E-ISSN 2218-273X

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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.

Item Type:	Article (Review)
Additional Information:	5136/90063
Uncontrolled Keywords:	thalassemia; β–thalassemia; epigenetics; DNA methylation; IGSF4; LARP2; BCL11A; KLF1; HBS1L-MYB; HBG-Xmn1
Subjects:	R Medicine > RB Pathology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Allied Health Sciences Kulliyyah of Allied Health Sciences > Department of Biomedical Science (Effective:1st July 2011)
Depositing User:	Dr Ridhwan Abdul Wahab
Date Deposited:	01 Jun 2021 16:43
Last Modified:	01 Jun 2021 16:43
URI:	http://irep.iium.edu.my/id/eprint/90063

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