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

描述（申请人提供）：未来五年的基本研究计划致力于完成一套新的目标，独特的INTERMAP国际代谢组学研究的多种尿液代谢物有关的血压（BP）和BP相关性状（营养，社会人口，拟人化，生物医学）-一个计划构思，开放，并由其在伦敦和芝加哥的高级合作首席研究员开发。在目前正在进行的资助NHLBI赠款（2007年2月1日-2011年1月31日），66尿代谢物（44已知的化学成分）已被确定，根据战略方法设定在以前（2006年）的赠款申请。这一策略需要从4,630名INTERMAP参与者中对10,000多份尿液样本进行配对取样，这些样本是基于与BP相关的特征，例如，较低和较高的植物蛋白质摄入量和Na/K摄入量;非裔美国人和其他美国人;北方和南方中国人，肥胖和瘦。对于每对对比样本，对已有的尿核磁共振（NMR）光谱（7100个峰/光谱）进行代谢组扫描，以识别尿代谢模式及其区分该对的特定代谢物。此外，根据这项研究策略，在所有4，630名参与者的两份尿液样本中定量了44种已知代谢物中的7种;其中5种与BP直接相关-丙氨酸，甲酸，马尿酸，4甲苯基硫酸盐，苯乙酰谷氨酰胺反向。在接下来的几年里，这一经过验证的策略将被连续利用，以实现从最近INTERMAP关于营养物- BP关系的研究结果中得出的一系列新的具体目标，即，确定尿代谢组学模式/特异性代谢物，区分摄入谷氨酸、甘氨酸、omega-3/omega-6 PFA及其特异性PFA、油酸/MFA、膳食Ca、Mg、P、非血红素Fe的较低和较高的INTERMAP参与者。此外，表征未知化学结构的代谢物。此外，在所有10，000 + INTERMAP尿液样本中，定量如此鉴定的选定代谢物，并评估其与BP的关系。为此目的，计划中的研究不仅依赖于现有的关于4 630名INTERMAP参与者（来自17个人口样本的40-59岁男女- 4名在日本; 3名在中华人民共和国; 2名在英国; 8名在美国）的广泛高质量数据。此外，如适用于上述目的，基础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，以补充已经用NMR实现的代谢分析。通过由此实现的数据分析，INTERMAP预计将增加一个新的研究信息维度，并在知识方面取得质的进步-在实践和理论上都具有潜在的重要性-关于人群范围内不良BP水平（高血压前期和高血压）的病因学。 公共卫生相关性：该研究项目使用了来自中国、日本、英国和美国17个随机人群样本的4，630名40-59岁女性和男性的广泛高质量数据：83种营养素的数据;尿钠、钾、钙、镁、23种氨基酸;通过现代生化/生物物理代谢组学技术鉴定的多种代谢物;社会人口统计学、拟人化和生物医学数据。重点是识别尿液中与血压（BP）和BP相关特征（营养，社会人口统计，拟人化，生物医学）相关的代谢物。这些数据有助于阐明生活方式和其他人类特征如何影响导致高血压前期和高血压流行的途径/机制-这些数据可以帮助预防和控制不良血压，心脏病和中风的关键风险因素。

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). PUBLIC HEALTH RELEVANCE: This research program uses extensive high-quality data for 4,630 women and men ages 40-59 from 17 random samples of populations in China, Japan, the United Kingdom, and the United States: data on 83 nutrients; urinary sodium, potassium, calcium, magnesium, 23 amino acids; multiple metabolites identified by modern biochemical/biophysical metabolomic techniques; sociodemographic, anthropomorphic, and biomedical data. The focus is on identification of metabolites in the urine that relate to blood pressure (BP) and BP-associated traits (nutritional, sociodemographic, anthropomorphic, biomedical). The data serve to clarify how lifestyles and other human traits influence the pathways/mechanisms leading to the epidemic of prehypertension and hypertension - - data that can help to prevent and control adverse BP, key risk factor for heart disease and stroke.