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、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，特别是艾滋病毒携带者。除了传统的风险因素，如身体偏高 体重指数、年龄、免疫激活和生活方式，饮食盐是导致 高血压的发展直接通过促进血管系统的病变和间接通过 免疫激活和炎症。盐的摄入量主要是由盐味敏感性和特定的遗传因素驱动的 味觉受体基因的变异。高盐摄入量是高血压的独立预测因子，动脉 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)的影响在有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饮食中盐的变化 摄入/消耗。目前尚不清楚盐味敏感性是否与SSBP相关。此外，中国的遗传变异 舌上皮钠通道(ENaC)与盐味敏感性有关，目前尚不清楚。因此， 这个项目的目的是：1.为了确定盐的味道敏感性是否与盐的摄入量有关，SSBP和 艾滋病毒携带者的炎症。我们假设盐味敏感度与SSBP和 发炎。为了实现这一点，将利用已知的SSBP的现有队列和炎性生物标志物 使用酶联免疫吸附试验和流式细胞仪进行测量，24小时食物回收和24小时尿量将被测量以评估 食盐摄入量。将使用系列稀释的盐溶液分析盐味敏感度，并与 HIV携带者和非HIV携带者之间的盐摄入量、SSBP和炎症。目的2.确定基因是否 在HIV中，ENaC的变化与盐味知觉、SSBP和高血压有关。我们假设 味觉受体基因的特定遗传变异，特别是ENaC基因，与盐味有关， SSBP和高血压。为了实现这一点，味觉受体基因的遗传测序将被执行以 确定HIV携带者和非HIV携带者的盐味敏感性和SSBP之间的联系。这些研究将 为未来的干预性研究生成假设。此外，长期目标是产生一个生物库 来自非洲的人的唾液和血液样本，用于未来的基因组，蛋白质组和代谢组分析 R01拨款申请。