鎌状赤血球症におけるF細胞分布の遺伝的および機能的洞察：ゲノムワイド関連解析アプローチ

Sickle cell anemia (SCA) is a severe hereditary disorder characterized by hemoglobin polymerization, vaso-occlusion, and chronic hemolysis. The distribution of F-cells, which retain fetal hemoglobin (HbF), plays a crucial role in mitigating disease severity. Genome-wide association studies (GWAS) have identified genetic determinants influencing F-cell persistence, yet the underlying mechanisms require further elucidation.

This study aims to analyse publicly available GWAS data to identify key genetic loci associated with F-cell distribution in SCA, assess their biological relevance, and explore potential therapeutic implications.

GWAS data were extracted from publicly available repositories and analysed for significant single nucleotide polymorphisms (SNPs) associated with F-cell levels. Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Transcription factor (TF) interactions, microRNA (miRNA) regulation, and protein-protein interactions (PPI) were explored to understand the molecular mechanisms governing HbF expression.

The study identified BCL11A, HBS1L-MYB, and β-globin cluster polymorphisms as primary regulators of F-cell distribution. Functional analysis highlighted pathways related to erythropoiesis, chromatin remodelling, and transcriptional regulation. miRNA-target interactions and epigenetic modifiers emerged as critical determinants of HbF persistence.

These findings provide insights into the genetic regulation of F-cell distribution, reinforcing the therapeutic potential of HbF modulation. Future studies should focus on functional validation and targeted interventions to enhance HbF expression in SCA.

The online version contains supplementary material available at 10.1007/s12288-025-02127-3.