Physiological Contributions of the Circadian Clock Gene Network to Blood Pressure Dipping and Non-Dipping Patterns in Hypertensive Nigerians: A Multi-Centre Chronobiological Study

Background: The circadian regulation of blood pressure follows a diurnal pattern with nocturnal dipping of approximately 10 to 20 percent, mediated by the autonomic nervous system and clock gene networks including CLOCK, BMAL1, PER, and CRY. Non-dipping, the absence of this nocturnal decline, substantially elevates cardiovascular risk and is more prevalent in populations of African descent. The molecular chronobiological basis of non-dipping has never been investigated in a Nigerian hypertensive cohort. Objectives: This study aims to characterise ambulatory blood pressure dipping status in hypertensive Nigerians across three geopolitical zones, quantify peripheral blood mononuclear cell expression of CLOCK, BMAL1, PER1, PER2, and CRY1 clock genes, measure melatonin and cortisol circadian profiles, and construct a mechanistic model linking clock gene dysregulation to non-dipping physiology. Methods: One hundred and fifty hypertensive adults from Sokoto, Enugu, and Akure will undergo 24-hour ambulatory blood pressure monitoring. Blood will be collected at six time points across 24 hours for clock gene expression by quantitative RT-PCR and hormonal profiling by immunoassay. Non-dipping will be defined as nocturnal decline below 10 percent. Logistic regression and time-series analysis will model clock gene-dipping associations. Expected Outcomes: Non-dippers are anticipated to exhibit blunted circadian amplitude in BMAL1 and PER2 expression and flattened melatonin and cortisol rhythms compared to dippers, with BMAL1 amplitude as the dominant molecular predictor. Conclusion: This multi-centre chronobiological study will generate original molecular physiological evidence explaining non-dipping hypertension in African populations. Keywords: circadian clock genes, blood pressure dipping, chronobiology, non-dipping hypertension, Nigeria.