Metabolomics-Measured Urinary Metabolites, Diet and BP, 17 Random Samples

描述（由申请人提供）：这个基础调查项目的未来五年致力于完成一套新的目标，即独特的INTERMAP国际代谢组学研究，研究与血压（BP）及其相关特征（营养，社会人口，拟人，生物医学）相关的多种尿代谢物。这是一个由伦敦和芝加哥的高级合作首席研究员构想，开放和发展的项目。在目前正在进行的NHLBI资助期间（2007年2月1日至2011年1月31日），基于先前（2006年）资助申请中制定的战略方法，已经确定了66种尿液代谢物（44种已知化学成分）。该策略需要对4630名INTERMAP参与者的10,000多个尿液样本进行配对采样，基于与BP相关的特征-例如，植物蛋白摄入量和Na/K摄入量的高低；非裔美国人和其他美国人；中国北方和南方，肥胖和瘦弱。对于每一对对比样本，我们对已有的尿液核磁共振（NMR）光谱（7100个峰/谱）进行代谢全范围扫描，以确定尿液代谢模式及其特异性代谢物。此外，根据该研究策略，在所有4,630名参与者的尿液样本中，对44种已知代谢物中的7种进行了量化；其中5种与BP -丙氨酸直接相关，甲酸酯、马尿酸酯、4种甲酰硫酸盐、苯乙酰谷氨酰胺与BP -丙氨酸负相关。在接下来的几年里，这一经过验证的策略将被连续地用于完成最近INTERMAP关于营养- BP关系的研究成果所衍生的一系列新的特定目标，即识别尿代谢组学模式/特定代谢物，区分INTERMAP参与者低摄入量和高摄入量：谷氨酸、甘氨酸、omega-3/omega-6 PFA及其特定PFA、油酸/MFA、膳食钙、镁、磷、非血红素铁。此外，表征未知化学结构的代谢物。进一步，在所有10,000+ INTERMAP尿液样本中，量化选定的代谢物，并评估它们与BP的关系。为此目的，预计的研究不仅依赖于已掌握的4,630名INTERMAP参与者（来自17个人口样本的40-59岁男女）的大量高质量数据——日本4人；中华人民共和国3人；联合王国2人；美国8人)。此外，根据上述目的，基本数据集将通过超高效液相色谱-飞行时间-质谱（UPLC - TOF - MS）分析进行扩展/增强，以补充已经通过核磁共振获得的代谢分析。随着数据分析的完成，INTERMAP预计将增加一个新的研究信息维度，并在广泛人群的不良血压水平（高血压前期和高血压）的发病机制方面取得定性的知识进展，这在实践和理论上都具有潜在的重要性。

DESCRIPTION (provided by applicant): The next five years of this basic investigative program are committed to accomplishing a new set of aims for the unique INTERMAP international metabolomics research on multiple urinary metabolites related to blood pressure (BP) and BP associated traits (nutritional, sociodemographic, anthropomorphic, biomedical) - a program conceived, opened up, and developed by its senior cooperating Principal Investigators in London and Chicago. During the years of the currently ongoing funded NHLBI grant (Feb. 1, 2007 - - Jan. 31, 2011), 66 urinary metabolites (44 of known chemical composition) have been identified, based on the strategic approach set down in the prior (2006) grant application. This strategy entailed paired sampling of the 10,000+ urinary specimens from the 4,630 INTERMAP participants, based on traits related to BP - - e.g., lower and higher vegetable protein intake and Na/K intake; African Americans and Other Americans; northern and southern Chinese, obese and lean. For each contrasting pair of samples, the urinary nuclear magnetic resonance (NMR) spectra already in hand (7100 peaks/spectrum) underwent metabolomewide scanning to identify the urinary metabolic pattern and its specific metabolites discriminating the pair. Further, per this research strategy, 7 of the 44 known metabolites were quantified in both urine specimens of all 4,630 participants; of these, 5 related to BP - - alanine directly, formate, hippurate, 4 cresyl sulphate, phenyl acetyl glutamine inversely. During the next years, this proven strategy is to be serially utilized to accomplished the new set of specific aims derived from recent INTERMAP research findings on nutrient - BP relations, i.e., identification of urinary metabolomic patterns/specific metabolites distinguishing INTERMAP participants with lower and higher intakes of: glutamic acid, glycine, omega-3/omega-6 PFA and their specific PFAs, oleic acid/MFA, dietary Ca, Mg, P, non-heme Fe. Further, characterize metabolites of unknown chemical structure. Further, quantify - - in all 10,000+ INTERMAP urine specimens - - selected metabolites so identified, and assess their relations to BP. For these purposes the projected research is relying not only on the extensive high-quality data already in hand on the 4,630 INTERMAP participants (women and men ages 40-59 from 17 population samples - - 4 in Japan; 3, People's Republic of China; 2, UK; 8, USA). In addition, as appropriate for the foregoing purposes, the basic data set is to be extended/enhanced with analyses by ultra performance liquid chromatography - time of flight - mass spectroscopy (UPLC - TOF - MS) to complement the metabolic profiling already achieved with NMR. With the data analyses thereby achieved, INTERMAP anticipates adding a new dimension of research information and achieving a qualitative advance in knowledge - - of potential importance both practically and theoretically - - on the etiophatogenesis of population wide adverse BP levels (prehypertensive and hypertensive).