Epigenetic Insights and Potential Modifiers as Therapeutic Targets in β–Thalassemia

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 DNA hypomethylation in the β–globin gene cluster significantly related to fetal hemoglobin (HbF) elevation. Histone modification reactivates γ-globin expression adults increases expression. Down-regulation γ–globin suppressor genes, i.e., BCL11A, KLF1, HBG-XMN1, HBS1L-MYB, SOX6, elevates HbF level. severity predictable through FLT1, ARG2, NOS2A, MAP3K5 NOS2A may predict patient’s response hydroxyurea, HbF-inducing drug. The transcription factors NRF2 BACH1 work with antioxidant enzymes, PRDX1, PRDX2, TRX1, SOD1, protect erythrocytes from oxidative damage, thus increasing their lifespan. A single β–thalassemia-causing mutation result different phenotypes, these are by IGSF4 LARP2 methylation as well long non-coding RNA levels. Finally, coinheritance α–thalassemia ameliorates clinical presentation. In conclusion, management currently limited genetic epigenetic approaches, numerous should further explored future.