ISCHEMIC STROKE IN AFRICANS: EXPLORING PROTECTIVE MECHANISMS AND THERAPEUTIC STRATEGIES THROUGH GENETIC AND EPIGENETIC INSIGHTS
OMOTAYO ALABA ELUWOLE1, PETER IFEOLUWA ADEGBOLA2
1. Department of Medical Pharmacology and Therapeutics, Faculty of Basic and Clinical Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria.
2. Department of Biochemistry and Forensic Science, Abiola Ajimobi Technical University, Ibadan, Nigeria
Afr. J Pharm Res Dev; Volume 18(1): 642-653 ; 2026
ABSTRACT
Stroke constitutes a primary cause of mortality and disability globally, with populations in Africa experiencing higher incidence and worse outcomes relative to other demographic groups. Although genetic and epigenetic mechanisms are progressively elucidating the factors influencing stroke susceptibility and recovery, African populations are notably underrepresented, comprising less than 5% participants in Genome-Wide Association Studies (GWAS), thereby constraining the scope and application of precision medicine. This review highlights key genetic and epigenetic factors influencing ischemic stroke in people of African ancestry, with emphasis on receptor-mediated pathways and therapeutic opportunities. We summarize genetic determinants such as APOL1, HDAC9, NOS3, and PDE4D, along with epigenetic regulators, including histone modifications, DNA methylation, and non-coding RNAs. These factors interact with environmental influences such as hypertension, diet, infections, and pollution to shape stroke risk and outcomes. We also examine receptor-driven mechanisms, including NMDA, AMPA, GABA, P2X7, cannabinoid, and VEGF signaling, which regulate excitotoxicity, oxidative stress, inflammation, and angiogenesis. Current and emerging receptor-targeted strategies, such as NMDA antagonists, GABAergic modulators, and P2X7 blockers, are evaluated for their translational potential. This review integrates receptor-mediated mechanisms with genetic and epigenetic insights, emphasizing African-specific determinants of stroke. We propose receptor-focused and precision medicine strategies to address Africa’s disproportionate stroke burden. Integrating African genetic and epigenetic data into stroke research is crucial for uncovering population-specific mechanisms and therapeutic targets. Advancing receptor-focused and precision medicine strategies could reduce the disproportionate stroke burden in Africa and improve global equity in stroke care.
Keywords: Ischemic stroke, gene-receptor interaction, africans, signaling pathways
Email of correspondence: omotayoeluwole@oauife.edu.ng;
https://doi.org/10.59493/ajopred/2026.1.24 ISSN: 0794-800X (print); 1596-2431 (online)