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

HIV 患者的盐味敏感性、遗传和血压盐敏感性

• 批准号: 10748253
• 负责人: Annet Kirabo
• 金额: $ 21.58万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-10 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10748253
• 关键词: Address; Adult; Affect; Africa; Africa South of the Sahara; African; African ancestry; Age; Applications Grants; Area; Automobile Driving; Biological Markers; Blood Pressure; Blood specimen; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Consumption; Country; Data; Development; Diet Habits; Dietary Assessment; Enzyme-Linked Immunosorbent Assay; Ethnic Origin; European; Exhibits; Flow Cytometry; Food; Future; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genetic study; Genomics; Genotype; Goals; HIV; HIV Seronegativity; HIV risk; Hour; Hypertension; IL17 gene; Individual; Inflammation; Inflammatory; Interferon Type II; Interleukin-6; Intervention Studies; Kidney Diseases; Laboratories; Life Style; Link; Literature; Measures; Myocardial Infarction; Participant; Pathogenesis; Pathologic; Pathway interactions; Perception; Persons; Population; Prevalence; Proteomics; Receptor Gene; Recommendation; Research; Risk; Risk Factors; Sodium Chloride; Stroke; Taste Buds; Taste Perception; Testing; Tongue; Urine; Vascular Diseases; World Health Organization; Zambia; arterial stiffness; biobank; blood pressure elevation; cohort; dietary salt; disorder prevention; epithelial Na+ channel; gene product; genetic association; genetic linkage; genetic variant; high body mass index; high risk population; immune activation; inflammatory marker; insight; low and middle-income countries; metabolomics; normotensive; preference; recruit; response; saliva sample; salt intake; salt sensitive hypertension

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.

项目摘要 高血压是中风、心脏病发作、肾病和死亡的危险因素。高血压患病率高 在撒哈拉以南非洲，特别是艾滋病毒感染者。除了传统的风险因素，如高身体 体重指数、年龄、免疫激活和生活方式，饮食中的盐是导致肥胖的驱动因素之一。 通过促进血管系统的病理变化直接发展高血压， 免疫激活和炎症。盐的摄入主要受盐的味觉敏感性和特定的遗传因素的影响。 味觉感受器基因的变异。高盐摄入量是高血压、动脉血压的独立预测因素 僵硬和心血管疾病。低收入和中等收入国家的食盐消费量普遍较高 包括赞比亚。盐对血压（BP）的影响在盐的个体中更为明显 血压敏感性（SSBP）SSBP是指血压的变化反映了膳食盐的变化 摄入/消耗。目前尚不清楚咸味敏感性是否与SSBP相关。此外，遗传变异 舌中与咸味敏感性相关的上皮钠通道（ENaC）是未知的。因此，我们认为， 该项目的目标是：1。为了确定盐的味觉敏感性是否与盐的摄入量有关，SSBP和 艾滋病毒感染者的炎症。我们假设咸味敏感性与SSBP相关， 炎症为了实现这一点，将利用已知SSBP的现有队列，并将炎症生物标志物 使用ELISA和流式细胞术测量，将测量24小时食物回忆和24小时尿液，以评估 食盐摄入量盐味敏感性将使用系列稀释的盐溶液进行分析，并与 盐摄入量，SSBP和炎症之间的人与艾滋病毒和没有。目标2.为了确定基因 ENaC的变异与盐味觉、SSBP和HIV高血压有关。我们假设 味觉受体基因中的特定遗传变异，特别是ENaC，与咸味有关， SSBP和高血压。为了实现这一点，将进行味觉受体基因的基因测序， 确定与盐的味道敏感性和SSBP在人与人之间的联系。这些研究将 为未来的干预性研究提出假设。此外，长期目标是建立一个生物库， 来自非洲的人的唾液和血液样本，用于未来的基因组，蛋白质组学和代谢组学分析， R 01赠款申请。