Metabolomics-Measured Urinary Metabolites, Diet & BP, 17 Population Samples: INTE

描述（由申请人提供）：背景：1997-99年期间，INTERMAP研究-在NHLBI的支持下-调查了来自日本（4个样本）、中华人民共和国（PRC）（3个样本）、英国（2个样本）和美国（8个样本）的17个不同人群样本的4，680名40-59岁男性和女性。采用标准化的质量控制方法，对所有参与者进行4次24小时饮食回忆，2次定时24小时尿液收集，8次血压（BP）测量，人体测量和问卷调查数据（关于社会人口统计学和生物医学特征）。食品、饮料和补充剂被转换为营养素（共83种），使用更新的、增强的、标准化的营养成分表（4张表，每个国家1张）。分析尿液中的Na、K、Ca、Mg、肌酐、白蛋白尿、氨基酸。位于英国伦敦的高质量中心实验室完成了所有尿液标本的核磁共振（NMR）光谱分析（4，680名参与者各2份，加上10%随机选择的盲法分离标本，用于外部质量控制）。所有数据都经过了广泛的质量控制检查，并在位于英国芝加哥和伦敦的两个INTERMAP国际协调中心进行了计算机化和安全化。目标：总体目标是-以一种高成本效益的方式-增加一个新的研究信息维度，从而在人群范围内不良BP水平（高血压前期和高血压）的病因学知识方面取得质的进步，即，发展一个新的流行病学领域的基础上，尿代谢产物，其中多种饮食和饮食相关因素影响血压。基于大量的、独特的高质量BP、营养、尿代谢物等数据的可用和可累积，具体目标是从现有的NMR谱加上质谱法和其他技术识别和量化与BP和与几种饮食代谢物中的每一种有区别地相关的尿代谢物。（植物蛋白、大豆蛋白、花生四烯酸、Na/K）、饮食相关的社会人口学（教育、种族）和人体测量（体重指数）因素影响BP。先进的生物信息学技术和生物化学方法将用于解决每个目标。重要性：BP问题是全人群的问题;等待个体发展为高血压，然后用药物治疗是一种不适当的策略。这项研究-通过确定与病因学途径有关的特定尿液代谢物，从而不良的饮食/生活方式模式导致人群范围内的不良BP水平-可以帮助制定预防/根除大规模BP问题的完全有效的策略。

DESCRIPTION (provided by applicant): BACKGROUND: During 1997-99, the INTERMAP Study - with NHLBI support - surveyed 4,680 men and women ages 40-59 from 17 diverse population samples in Japan (4 samples), the Peoples Republic of China (PRC) (3 samples), the UK (2 samples), and the USA (8 samples). With standardized, quality-controlled methods, 4 24-hour dietary recalls, 2 timed 24-hour urine collections, 8 blood pressure (BP) measurements, anthropometric, and questionnaire data (on sociodemographic and biomedical traits) were accrued for all participants. Foods, beverages, and supplements were converted to nutrients (83 total) with use of up-dated, enhanced, standardized tables on nutrient composition (4 tables, 1/country). Urines were analyzed for Na, K, Ca, Mg, creatinine, albuminuria, amino acids. A high-quality central laboratory in London, England completed nuclear magnetic resonance (NMR) spectroscopic analyses of all urine specimens (2 from each of the 4, 680 participants plus 10% randomly selected, blinded split specimens for external quality control). All data underwent extensive quality control checks and were computerized and secured at the two INTERMAP International Coordinating Centers in Chicago and London, England. AIMS: Overall aim is - in a highly cost effective way - to add a new dimension of research information and thereby achieve a qualitative advance in knowledge on the etiopathogenesis of population-wide adverse BP levels (prehypertensive and hypertensive), i.e., develop a new epidemiologic area based on the urinary metabolic products whereby multiple dietary and diet-related factors influence BP. Based on the vast, unique array of high quality BP, nutritional, urinary metabolite, etc. data available and accruable, the specific aims are to identify and quantify - from NMR spectra in hand plus mass spectrometry and other techniques - urinary metabolites discriminatively related to BP and to each of several dietary (vegetable protein, soy protein, arachidonic acid, Na/K), diet-related sociodemographic (education, ethnicity) and anthropometric (body mass index) factors impacting BP. Advanced bioinformatics techniques and biochemical methods are to be used to address each aim. SIGNIFICANCE: The BP problem is population-wide; waiting for individuals to develop hypertension and then treating them with drugs is an inadequate strategy. This study - by identifying specific urinary metabolites implicated in the etiologic pathways whereby adverse dietary/lifestyle patterns lead to population-wide adverse BP levels - can help create fully effective strategies for prevention/eradication of the mass BP problem.