Human metabolic phenotype diversity and its association with diet and blood pressure
Human metabolic phenotype diversity and its association with diet and blood pressure
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DOI：
10.1038/nature06882
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发表时间：
2008-05-15
期刊：
影响因子：
64.8
通讯作者：
Elliott, Paul
中科院分区：
文献类型：
--
作者：
Holmes, Elaine;Loo, Ruey Leng;Elliott, Paul
代谢表型是多种因素-饮食、其他生活方式/环境、肠道微生物和遗传（1 - 3）之间相互作用的产物。我们使用一个大规模的探索性分析方法，研究代谢表型的变化，在四个人群中，基于H-1 NMR光谱。然后将人群间的代谢物歧视与血压个体的数据联系起来，血压是冠心病和中风的主要风险因素（全球死亡率的主要原因（4））。我们分析了来自INTERMAP流行病学研究（5）的4，630名参与者的两份24小时尿液样本的光谱，涉及中国，日本，英国和美国的17个40 - 59岁的人群样本。我们发现，东亚和西方人群样本的尿代谢产物排泄模式存在显著差异（P <10（-16）），饮食、饮食相关的主要风险因素和冠心病/中风发生率存在差异，中国/日本人群的代谢表型以及饮食中植物/动物蛋白和血压存在差异的亚组也存在显著差异（6）。在鉴别代谢物中，我们对四种代谢物进行了定量，并在多元回归分析中显示了个体平均24小时尿甲酸排泄量与血压的相关性（P <0.05至P <0.0001）。丙氨酸（直接）和马尿酸（反向）的平均24小时尿排泄，反映了饮食和肠道微生物活性（2，7），也与个体的血压相关。代谢表型应用于高质量的流行病学数据提供了潜在的发展领域的病因学知识，涉及发现新的生物标志物相关的心血管疾病的风险。
Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic(1-3). We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on H-1 NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide(4)). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study(5), involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure(6). Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities(2,7), are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.