Genetic modifications of EGLN1 reactivate HbF production in β⁰-thalassemia/HbE.

ABSTRACT: Reactivation of fetal hemoglobin (HbF, α₂γ₂) potentially alleviates clinical presentation in β-thalassemia. Prolyl hydroxylase domain enzymes (PHDs) play roles in the canonical oxygen-sensing pathway and maintain the stability of cellular hypoxia-inducible factor α (HIF-α) in response to low oxygen levels or hypoxia. Pharmacological inhibition of PHDs has been shown to increase HbF production in erythroid progenitors derived from healthy donors. Here, we demonstrated the relationship between PHD2, the main PHD isoform, and clinical phenotypes in β⁰-thalassemia/HbE disease. Although the targeted sequencing annotated several common variants within EGLN1, the gene encoding PHD2, none of these variants were located in the functional domains of PHD2 and w

SUBMITTER: Jan-Ngam V 

PROVIDER: S-EPMC11459010 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature