Inflammatory factors, genes and stress induced pressure natriuresis in youth

炎症因素、基因和应激诱发的青少年压力尿钠

• 批准号: 7130232
• 负责人: HAIDONG ZHU
• 金额: $ 14.65万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7130232
• 关键词: C reactive protein; adolescence (12-20); behavioral /social science research tag; blood pressure; clinical research; electrolyte balance; essential hypertension; genetic susceptibility; genotype; homeostasis; human genetic material tag; human subject; immunogenetics; inflammation; interleukin 6; linkage disequilibriums; psychological stressor; psychoneuroimmunology; psychosomatic disorders; saluresis; single nucleotide polymorphism; urination

DESCRIPTION (provided by applicant): Impaired stress-induced pressure natriuresis is defined as an increase in blood pressure (BP) during a period of extended stress without an adequate compensatory increase in urinary sodium excretion (UNaV) to contribute to the return of systolic BP (SBP) to pre-stress levels. Studies on animal models and human subjects reveal that BP increase under stress depends significantly on interleukin-6 (IL-6). IL-6 is a multi- functional cytokine that acts through a receptor comprising two subunits, IL-6 receptor (IL-6R) and gp130 cytokine signal transducer (gp130), and releases C-reactive protein (CRP). The main goal thus is to determine the role of the IL-6 pathway on the dynamic regulation of sodium homeostasis and BP under stress in normotensive youth. To achieve this goal, this proposed study will take two approaches: comprehensive analyses of genetic variability and measurements of circulating levels. Therefore, the specific aims are to test the following hypotheses: 1. Youth with unfavorable genotypes or haplotypes of the genes in the IL-6 pathway compared to those without will show a reduced stress-induced increase in UNaV and delayed SBP recovery following stress. 2. Plasma IL-6 and CRP levels in response to stress will be inversely related to stress-induced UNaV in youth, but positively related to recovery SBP following stress in youth. A total of 500 subjects aged 15-19 yrs will be studied which include an equal number of whites and blacks, boys and girls. All subjects have been previously tested with an extended stress protocol including a recovery period. Single nucleotide polymorphisms (SNPs) in the IL-6 and CRP genes will be systematically examined in these subjects using tagging SNP and haplotype approaches. Functional SNPs of the IL-6, IL6R, gp130 and CRP genes will also be studied. Buccal cell DNA from the parents of these youth will be collected to facilitate (1) haplotype reconstruction and analyses and (2) transmission disequilibrium tests (TDTs). Plasma levels of IL-6 and CRP will be examined in a subsample of 109 subjects. This research will provide novel insight into the interactions between stress, inflammation, and genetics, and their contribution to the pathogenesis of essential hypertension. The project aims to investigate the influence of inflammation, stress and genes on the body's ability to release sodium. Understanding the connections between stress, inflammation, and genes will provide a fresh approach into evaluating risk factors for high blood pressure.

描述（由申请人提供）：压力诱导的压力纳特里雷仪受损被定义为在延长压力期间血压（BP）的升高，而没有足够的尿钠排泄（UNAV）补偿性增加以有助于收缩BP的回报（SBP）到预压水平。关于动物模型和人类受试者的研究表明，压力下的BP增加显着取决于白介素6（IL-6）。 IL-6是一种多功能细胞因子，它通过包含两个亚基IL-6受体（IL-6R）和GP130细胞因子信号传感器（GP130）的受体起作用，并释放C反应性蛋白（CRP）。因此，主要目标是确定IL-6途径在正常青年时压力下的钠稳态和BP动态调节的作用。为了实现这一目标，这项拟议的研究将采用两种方法：综合分析遗传变异性和循环水平的测量。因此，具体目的是检验以下假设：1。与没有的基因相比，IL-6途径中具有不利基因型或单倍型的青年将显示出应力诱导的UNAV降低，而在压力后，UNAV的增加和延迟的SBP恢复延迟。 2。响应压力的血浆IL-6和CRP水平将与青年人的压力引起的UNAV成反比，但与青少年压力后的恢复SBP呈正相关。总共将研究500名15-19岁的受试者，其中包括相等数量的白人和黑人，男孩和女孩。所有受试者先前均已使用扩展的应力方案进行了测试，包括恢复期。 IL-6和CRP基因中的单核苷酸多态性（SNP）将在这些受试者中使用标记SNP和单倍型方法在这些受试者中进行系统检查。还将研究IL-6，IL6R，GP130和CRP基因的功能性SNP。将收集这些青年父母的颊细胞DNA，以促进（1）单倍型重建和分析以及（2）传播不平衡测试（TDTS）。 IL-6和CRP的血浆水平将在109名受试者的子样本中检查。这项研究将为应力，炎症和遗传学之间的相互作用及其对基本高血压发病机理的贡献提供新的见解。该项目旨在研究炎症，压力和基因对人体释放钠的能力的影响。了解压力，炎症和基因之间的联系将为评估高血压危险因素提供新的方法。