Epigenetic Regulation of Gene Expression in Sickle Cell Disease Complications: DNA Methylation Analysis in Patients from Ibadan

Beyond the primary genetic mutation in the HBB gene, epigenetic modifications including DNA methylation are emerging as important modulators of sickle cell disease (SCD) clinical heterogeneity, influencing foetal haemoglobin reactivation, inflammatory gene expression, and organ damage pathways. Despite the relevance of SCD epigenomics, no epigenome-wide studies have been conducted in Nigerian SCD populations. This study investigated genome-wide DNA methylation profiles in SCD patients with contrasting clinical severity phenotypes at the University College Hospital, Ibadan, Oyo State. Sixty HbSS patients were stratified into severe (frequent vaso-occlusive crises, acute chest syndrome, or stroke) and mild (fewer than two crises per year, no major organ complications) phenotype groups. Genomic DNA from peripheral blood mononuclear cells was subjected to bisulphite conversion and hybridisation on the Illumina Infinium MethylationEPIC array. Differentially methylated regions (DMRs) were identified using the minfi and bumphunter R packages. Significant hypomethylation was observed at the BCL11A locus in mild-phenotype patients, consistent with its role in HbF regulation. Immune-related gene loci showed differential methylation between severity groups. These findings advance understanding of epigenetic contributors to SCD heterogeneity in the Nigerian context. Keywords: sickle cell disease, DNA methylation, epigenomics, foetal haemoglobin, BCL11A