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

背景：在1997- 1999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（3个样本）、英国（2个样本）和美国（8个样本）17个不同人群样本的4,680名年龄在40-59岁之间的男性和女性。采用标准化、质量控制的方法，对所有参与者进行了4次24小时饮食回顾、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（关于社会人口统计学和生物医学特征）。使用最新的、增强的、标准化的营养成分表（4张表，1个国家），将食品、饮料和补充剂转换为营养素（总共83种）。分析尿中Na、K、Ca、Mg、肌酐、蛋白尿、氨基酸。英国伦敦一家高质量的中心实验室完成了所有尿液样本的核磁共振（NMR）光谱分析（4680名参与者中每人2份，外加10%随机选择的盲法分离样本，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，并在芝加哥和英国伦敦的两个INTERMAP国际协调中心电脑化和保管。目的：总体目标是以高成本效益的方式增加研究信息的新维度，从而在全人群不良血压水平（高血压前期和高血压）的发病机制方面取得质的进展，即基于多种饮食和饮食相关因素影响血压的尿代谢产物开发一个新的流行病学领域。基于大量、独特的高质量血压、营养、尿液代谢物等数据，具体目标是识别和量化——从手中的核磁共振光谱加上质谱和其他技术——与血压和几种饮食（植物蛋白、大豆蛋白、花生四烯酸、Na/K）、饮食相关的社会人口统计学（教育、种族）和人体测量学（体重指数）影响血压的因素有区别地相关的尿液代谢物。先进的生物信息学技术和生化方法将用于解决每个目标。意义：BP问题是全局性的；等待个体患上高血压，然后用药物治疗是一种不充分的策略。本研究通过确定与不良饮食/生活方式导致人群不良血压水平的病因途径相关的特定尿液代谢物，有助于制定预防/根除大规模血压问题的全面有效策略。

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.