Epigenetic Insights and Potential Modifiers as Therapeutic Targets in -Thalassemia.

Thalassemia, an inherited quantitative globin disorder, consists of two types, α- and -thalassemia. -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., , , , , and elevates the HbF level. -thalassemia severity is predictable through , , , and gene expression. and may predict the -thalassemia patient's response to hydroxyurea, a HbF-inducing drug. The transcription factors NRF2 and work with antioxidant enzymes, i.e., , , , and , to protect erythrocytes from oxidative damage, thus increasing their lifespan. A single -thalassemia-causing mutation can result in different phenotypes, and these are predictable by and methylation as well as long non-coding RNA expression levels. Finally, the coinheritance of -thalassemia with α-thalassemia ameliorates the -thalassemia clinical presentation. In conclusion, the management of -thalassemia is currently limited to genetic and epigenetic approaches, and numerous factors should be further explored in the future.