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 在撒哈拉以南非洲地区，特别是艾滋病毒感染者。除了高身体等传统风险因素外 体重指数、年龄、免疫激活和生活方式，膳食盐是导致肥胖的驱动因素之一 高血压的发展直接通过促进脉管系统的病理变化而间接通过 免疫激活和炎症。盐的摄入量主要由盐味敏感性和特定遗传驱动 味觉受体基因的变异。高盐摄入量是高血压、动脉粥样硬化的独立预测因素 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) 的影响在吃盐的个体中更为明显 血压敏感性（SSBP）。 SSBP 是指血压变化反映膳食盐的变化 摄入/消耗。目前尚不清楚盐味敏感性是否与 SSBP 相关。此外，遗传变异 与盐味敏感性相关的舌头上皮钠通道（ENaC）尚不清楚。所以， 该项目的目的是： 1. 确定盐味敏感性是否与盐摄入量、SSBP 和 HIV感染者的炎症。我们假设盐味敏感性与 SSBP 相关，并且 炎。为了实现这一目标，将利用已知 SSBP 的现有队列和炎症生物标志物 使用 ELISA 和流式细胞术进行测量，将测量 24 小时食物回忆和 24 小时尿液来评估 膳食盐摄入量。将使用连续稀释的盐溶液来分析盐味敏感性，并与 HIV感染者和未感染者之间的盐摄入量、SSBP和炎症。目标 2. 确定是否遗传 ENaC 的变化与 HIV 患者的盐味觉、SSBP 和高血压有关。我们假设 味觉受体基因（尤其是 ENaC）的特定遗传变异与盐味相关， SSBP 和高血压。为了实现这一目标，将对味觉受体基因进行基因测序 确定感染和未感染艾滋病毒的人与盐味敏感性和 SSBP 的联系。这些研究将 为未来的介入研究提出假设。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、蛋白质组和代谢组分析 R01 拨款申请。