Salt taste sensitivity, genetics and salt sensitivity of blood pressure in HIV

项目摘要

Project Abstract Hypertension is a risk factor for stroke, heart attack, kidney disease and death. Hypertension prevalence is high in sub-Saharan Africa, specifically in persons living with HIV. Apart from traditional risk factors such as high body mass index, age, immune activation and lifestyle, dietary salt is one of the driving factors contributing to the development of hypertension directly by promoting pathological changes in the vasculature and indirectly through immune activation and inflammation. Salt intake is driven mainly by salt taste sensitivity and specific genetic variations in the taste receptor genes. High salt consumption is an independent predictor of hypertension, arterial stiffness and cardiovascular disease. Salt consumption is generally high in Low- and Middle-Income Countries including Zambia. The effects of salt on blood pressure (BP) are more pronounced in individuals with salt sensitivity of blood pressure (SSBP). SSBP is when changes in BP mirror changes in dietary salt intake/depletion. It is not clear if salt taste sensitivity correlates with SSBP. Furthermore, genetic variations in the epithelial sodium channel (ENaC) in the tongue associated with salt taste sensitivity are unknown. Therefore, the aims of this project are to: 1. To determine if salt taste sensitivity is associated with salt intake, SSBP and inflammation in persons with HIV. We hypothesize that salt taste sensitivity correlates with SSBP and inflammation. To achieve this, an existing cohort with known SSBP will be utilized and inflammatory biomarkers measured using ELISA and flow cytometry, 24-hr food recall and 24-hour urine will be measured to assess dietary salt intake. Salt taste sensitivity will be analysed using serial diluted salt solutions, and compared with salt intake, SSBP and inflammation between people with and without HIV. Aim 2. To determine if genetic variations in ENaC are associated with salt taste perception, SSBP and hypertension in HIV. We hypothesize that specific genetic variations in the taste receptor genes particularly for ENaC are associated with salt taste, SSBP and hypertension. To achieve this, genetic sequencing of taste receptor genes will be performed to determine linkage with salt taste sensitivity and SSBP in persons with and without HIV. These studies will generate hypotheses for future interventional studies. In addition, the long-term goal is to generate a biobank of saliva and blood samples of persons from Africa for future genomic, proteomic and metabolomic analysis in an R01 grant application.