Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–Thalassemia
Thalassemia, an inherited quantitative globin disorder, consists of two types, α– and <i>β</i>–thalassemia. <i>β</i>–thalassemia is a heterogeneous disease that can be asymptomatic, mild, or even severe. Considerable research has focused on investigating its underlying etiolo...
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doaj-77857f8e357349df896c322d6cde0f722021-06-01T00:22:36ZengMDPI AGBiomolecules2218-273X2021-05-011175575510.3390/biom11050755Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–ThalassemiaNur Atikah Zakaria0Md Asiful Islam1Wan Zaidah Abdullah2Rosnah Bahar3Abdul Aziz Mohamed Yusoff4Ridhwan Abdul Wahab5Shaharum Shamsuddin6Muhammad Farid Johan7Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaDepartment of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaDepartment of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaDepartment of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaDepartment of Neurosciences, School of Medical Sciences, University Sains Malaysia, Kubang Kerian 16150, MalaysiaDepartment of Biomedical Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan 25200, MalaysiaSchool of Health Sciences, University Sains Malaysia, Kubang Kerian 16150, MalaysiaDepartment of Haematology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, MalaysiaThalassemia, an inherited quantitative globin disorder, consists of two types, α– and <i>β</i>–thalassemia. <i>β</i>–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., <i>BCL11A</i>, <i>KLF1</i>, <i>HBG-XMN1</i>, <i>HBS1L-MYB</i>, and <i>SOX6,</i> elevates the HbF level. <i>β</i>–thalassemia severity is predictable through <i>FLT1</i>, <i>ARG2</i>, <i>NOS2A</i>, and <i>MAP3K5</i> gene expression. <i>NOS2A</i> and <i>MAP3K5</i> may predict the <i>β</i>–thalassemia patient’s response to hydroxyurea, a HbF-inducing drug. The transcription factors NRF2 and <i>BACH1</i> work with antioxidant enzymes, i.e., <i>PRDX1</i>, <i>PRDX2</i>, <i>TRX1</i>, and <i>SOD1</i>, to protect erythrocytes from oxidative damage, thus increasing their lifespan. A single <i>β</i>–thalassemia-causing mutation can result in different phenotypes, and these are predictable by <i>IGSF4</i> and <i>LARP2</i> methylation as well as long non-coding RNA expression levels. Finally, the coinheritance of <i>β</i>–thalassemia with α–thalassemia ameliorates the <i>β</i>–thalassemia clinical presentation. In conclusion, the management of <i>β</i>–thalassemia is currently limited to genetic and epigenetic approaches, and numerous factors should be further explored in the future.https://www.mdpi.com/2218-273X/11/5/755thalassemia<i>β</i>–thalassemiaepigeneticsDNA methylation<i>IGSF4</i><i>LARP2</i> |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nur Atikah Zakaria Md Asiful Islam Wan Zaidah Abdullah Rosnah Bahar Abdul Aziz Mohamed Yusoff Ridhwan Abdul Wahab Shaharum Shamsuddin Muhammad Farid Johan |
spellingShingle |
Nur Atikah Zakaria Md Asiful Islam Wan Zaidah Abdullah Rosnah Bahar Abdul Aziz Mohamed Yusoff Ridhwan Abdul Wahab Shaharum Shamsuddin Muhammad Farid Johan Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–Thalassemia Biomolecules thalassemia <i>β</i>–thalassemia epigenetics DNA methylation <i>IGSF4</i> <i>LARP2</i> |
author_facet |
Nur Atikah Zakaria Md Asiful Islam Wan Zaidah Abdullah Rosnah Bahar Abdul Aziz Mohamed Yusoff Ridhwan Abdul Wahab Shaharum Shamsuddin Muhammad Farid Johan |
author_sort |
Nur Atikah Zakaria |
title |
Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–Thalassemia |
title_short |
Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–Thalassemia |
title_full |
Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–Thalassemia |
title_fullStr |
Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–Thalassemia |
title_full_unstemmed |
Epigenetic Insights and Potential Modifiers as Therapeutic Targets in <i>β</i>–Thalassemia |
title_sort |
epigenetic insights and potential modifiers as therapeutic targets in <i>β</i>–thalassemia |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2021-05-01 |
description |
Thalassemia, an inherited quantitative globin disorder, consists of two types, α– and <i>β</i>–thalassemia. <i>β</i>–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., <i>BCL11A</i>, <i>KLF1</i>, <i>HBG-XMN1</i>, <i>HBS1L-MYB</i>, and <i>SOX6,</i> elevates the HbF level. <i>β</i>–thalassemia severity is predictable through <i>FLT1</i>, <i>ARG2</i>, <i>NOS2A</i>, and <i>MAP3K5</i> gene expression. <i>NOS2A</i> and <i>MAP3K5</i> may predict the <i>β</i>–thalassemia patient’s response to hydroxyurea, a HbF-inducing drug. The transcription factors NRF2 and <i>BACH1</i> work with antioxidant enzymes, i.e., <i>PRDX1</i>, <i>PRDX2</i>, <i>TRX1</i>, and <i>SOD1</i>, to protect erythrocytes from oxidative damage, thus increasing their lifespan. A single <i>β</i>–thalassemia-causing mutation can result in different phenotypes, and these are predictable by <i>IGSF4</i> and <i>LARP2</i> methylation as well as long non-coding RNA expression levels. Finally, the coinheritance of <i>β</i>–thalassemia with α–thalassemia ameliorates the <i>β</i>–thalassemia clinical presentation. In conclusion, the management of <i>β</i>–thalassemia is currently limited to genetic and epigenetic approaches, and numerous factors should be further explored in the future. |
topic |
thalassemia <i>β</i>–thalassemia epigenetics DNA methylation <i>IGSF4</i> <i>LARP2</i> |
url |
https://www.mdpi.com/2218-273X/11/5/755 |
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