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

描述(由申请者提供)：这个基础研究计划的未来五年致力于实现INTERMAP国际代谢组学研究的一套新目标，该研究针对与血压相关的多种尿代谢物以及与血压相关的特征(营养、社会人口学、拟人学、生物医学)-该计划由伦敦和芝加哥的高级合作首席研究员构思、开放和开发。在目前正在进行的NHLBI赠款期间(2007年2月1日至2011年1月31日)，根据先前(2006年)赠款申请中制定的战略方法，已鉴定出66种尿代谢物(44种已知化学成分)。这一战略需要对4,630名INTERMAP参与者的10,000多份尿样进行配对抽样，这些样本基于与BP相关的特征--例如，植物蛋白摄入量越来越低和更高，钠/钾摄入量越来越高；非裔美国人和其他美国人；中国北方和南方、肥胖和瘦削。对于每一对对比样本，手头已有的尿液核磁共振(核磁共振)谱(7100个峰/谱)进行了全代谢扫描，以确定区分这两个样本的尿代谢模式及其特定代谢物。此外，根据这一研究策略，在所有4630名参与者的两个尿样中，对44种已知代谢物中的7种进行了定量；其中5种与BP-丙氨酸直接相关，甲酸盐、马尿酸、4甲酚硫酸盐、苯乙酰谷氨酰胺与之相反。在接下来的几年里，这一成熟的策略将被连续用于实现根据INTERMAP最近关于营养与血压关系的研究结果得出的一套新的特定目标，即识别尿代谢组模式/特定代谢物，以区分INTERMAP参与者较低和较高的谷氨酸、甘氨酸、omega-3/omega-6 PFA及其特定PFA、油酸/MFA、饮食中的钙、镁、磷、非血红素铁的摄入量。此外，对化学结构未知的代谢物进行表征。此外，在所有10,000多个INTERMAP尿样中，对如此确定的选定代谢物进行量化，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4630名国际监测和评估计划参与者的大量高质量数据(17个人口样本中年龄在40-59岁的女性和男性--日本4人；中国共和国3人；英国2人；美国8人)。此外，在适用于上述目的的情况下，将利用超高效液相色谱-飞行时间-质谱仪(UPLC-TOF-MS)对基本数据集进行扩展/增强，以补充已经通过核磁共振实现的代谢概况。有了这样的数据分析，INTERMAP预计将增加一个新的研究信息维度，并在关于人群范围内不良血压水平(高血压前期和高血压)的病因的知识--具有潜在的实际和理论重要性--方面取得质的进展。

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).