Epigenetic Regulation of Inflammatory Gene Expression in Patients with Type 2 Diabetes Mellitus and Cardiovascular Comorbidities in South West Nigeria

The epigenetic regulation of inflammatory pathways through DNA methylation and histone modification represents a frontier area of research with profound implications for understanding the molecular basis of diabetic cardiovascular complications. This study investigates epigenetic modifications at promoter regions of key pro-inflammatory genes, specifically TNF-alpha, IL-6, and NF-kB, in peripheral blood mononuclear cells of type 2 diabetic patients with and without established cardiovascular disease in South West Nigeria. A multi-site case-control design was employed across three tertiary centres in Lagos, Ogun, and Oyo States, recruiting 150 T2DM patients with cardiovascular comorbidities, 150 without, and 100 non-diabetic controls. Genome-wide methylation was assessed by reduced representation bisulfite sequencing, and targeted promoter methylation was quantified by pyrosequencing. Histone H3K27 acetylation at inflammatory gene loci was characterised by chromatin immunoprecipitation sequencing. Clinical glycaemic data including HbA1c, disease duration, and anti-diabetic therapy were integrated into epigenome-wide association modelling. This study constitutes the first epigenomic profiling of T2DM inflammatory pathways in a Nigerian population and will provide original biochemical frameworks for understanding ethnicity-specific diabetic cardiovascular risk. Findings will contribute novel theoretical models to the global literature on diabetic epigenomics. Keywords: epigenetics, DNA methylation, type 2 diabetes, inflammatory genes, cardiovascular disease.