International Journal of Molecular Medical Science, 2024, Vol.14, No.4, 203-215 http://medscipublisher.com/index.php/ijmms 203 Systematic Review Open Access Epigenetic Regulatory Mechanisms in Sickle Cell Anemia ManmanLi Hainan Institute of Biotechnology, Haikou, 570206, Hainan, China Corresponding email: manan.li@hibio.org International Journal of Molecular Medical Science, 2024, Vol.14, No.4 doi: 10.5376/ijmms.2024.14.0023 Received: 23 May, 2024 Accepted: 28 Jun., 2024 Published: 09 Jul., 2024 Copyright © 2024 Li, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Li M.M., 2024, Epigenetic regulatory mechanisms in sickle cell anemia, International Journal of Molecular Medical Science, 14(4): 203-215 (doi: 10.5376/ijmms.2024.14.0023) Abstract Epigenetics plays a critical role in gene regulation and disease development by influencing gene expression without altering the DNA sequence. Sickle Cell Anemia (SCA) is a genetic disorder caused by a single gene mutation, and epigenetic mechanisms are crucial in modulating the pathophysiology of SCA. This study explores the role of epigenetics in SCA, with a particular focus on the epigenetic regulation of fetal hemoglobin (HbF), histone modifications, DNA methylation, and the role of non-coding RNAs. The study also examines how these epigenetic regulatory mechanisms influence the clinical manifestations of SCA and discusses the potential of these mechanisms as therapeutic targets. Additionally, the potential functions of non-coding RNAs in regulating gene expression in SCA are summarized. The findings indicate that the epigenetic regulation of HbF expression is essential in alleviating SCA symptoms, while histone modifications and DNA methylation play significant roles in regulating gene expression in SCA. Furthermore, non-coding RNAs are also involved in the gene regulatory networks of SCA. By delving into the epigenetic regulatory mechanisms in SCA, this study provides a theoretical basis for developing novel therapeutic strategies. These insights not only contribute to understanding the molecular basis of SCA but also offer new perspectives for developing epigenetic therapies targeting HbF, thereby improving the prognosis of SCA patients. Keywords Sickle cell anemia; Epigenetic regulation; Fetal hemoglobin; Histone modifications; DNA methylationg 1 Introduction Sickle Cell Anemia (SCA) is a hereditary blood disorder caused by a mutation in the β-globin gene, leading to the production of abnormal hemoglobin known as hemoglobin S (HbS). This mutation results in the polymerization of HbS under deoxygenated conditions, causing red blood cells (RBCs) to assume a sickled shape. These sickled RBCs are rigid and fragile, leading to hemolytic anemia and various complications such as vaso-occlusive crises, chronic inflammation, and organ damage (Kato et al., 2018; Nader et al., 2020; Nader et al., 2021). The disease is characterized by a wide range of acute and chronic complications, including pain episodes, acute chest syndrome, stroke, and chronic kidney disease (Kato et al., 2018; Sundd et al., 2019). Epigenetics refers to heritable changes in gene expression that do not involve alterations in the DNA sequence. These changes can be influenced by various factors, including environmental stimuli, and can significantly impact disease progression and severity (Mason, 2024). In the context of SCA, epigenetic mechanisms such as DNA methylation, histone modification, and non-coding RNA regulation play crucial roles in modulating the expression of genes involved in inflammation, oxidative stress, and vascular function (Sundd et al., 2019; Conran and Paula, 2020). These epigenetic modifications can influence the clinical phenotype of SCA, potentially offering new avenues for therapeutic intervention. Understanding the epigenetic regulatory mechanisms in Sickle Cell Anemia (SCA) is crucial. It provides insights into the differences in disease severity and treatment responses among patients. Moreover, it offers possibilities for developing strategies to modify epigenetic marks, which could alleviate disease symptoms and improve patient outcomes. Research into the epigenetics of SCA also contributes to the broader field of epigenetics, revealing how genetic and environmental factors interact to influence complex diseases (Inusa et al., 2019; Conran and Paula, 2020). This study comprehensively reviews the current understanding of epigenetic regulatory mechanisms in SCA. It includes exploring how epigenetic modifications influence disease progression, the potential of epigenetic
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