Genetic Polymorphisms in the Renin-Angiotensin-Aldosterone System and Their Interaction with Dietary Sodium Intake in Determining Hypertension Susceptibility Among Yoruba Adults in South West Nigeria

Background: Hypertension in sub-Saharan Africa exhibits distinctive epidemiological and pathophysiological features, including a higher prevalence of salt-sensitive hypertension and earlier end-organ damage. Polymorphisms in renin-angiotensin-aldosterone system genes, including the angiotensin-converting enzyme insertion-deletion and angiotensinogen M235T variants, may modulate blood pressure response to dietary sodium in African populations. Nigerian pharmacogenomic and nutrigenetic data addressing these interactions are largely absent. Objectives: This study aims to genotype renin-angiotensin-aldosterone system gene polymorphisms, quantify dietary sodium intake by 24-hour urinary sodium excretion, and model gene-diet interactions predicting hypertension severity and salt sensitivity in Yoruba adults in South West Nigeria, using a case-control design nested within a community-based cohort. Methods: Two hundred hypertensive Yoruba adults and two hundred normotensive controls will be recruited from Osun and Oyo States. DNA will be extracted from buffy coat and genotyped by PCR-restriction fragment length polymorphism. Twenty-four-hour urine will be collected for sodium and creatinine quantification. Blood pressure will be measured by automated 24-hour ambulatory monitoring. Gene-environment interaction terms will be incorporated into multilevel logistic regression models. Expected Outcomes: Carriers of the angiotensin-converting enzyme DD genotype with high urinary sodium excretion are anticipated to exhibit the highest hypertension risk, with a statistically significant gene-sodium interaction term. Conclusion: This study will generate original nutrigenetic evidence relevant to precision hypertension management in Yoruba populations. Keywords: renin-angiotensin-aldosterone system, gene polymorphism, dietary sodium, salt-sensitive hypertension, Yoruba.