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Human metabolic phenotype diversity and its association with diet and blood pressure

Holmes, Elaine, Loo, Ruey Leng, Stamler, Jeremiah, Bictash, Magda, Yap, Ivan K. S., Chan, Queenie, Ebbels, Timothy, De Iorio, Maria, Brown, Ian J., Veselkov, Kirill A., and others. (2008) Human metabolic phenotype diversity and its association with diet and blood pressure. Nature, 453 (7193). pp. 396-400. ISSN 0028-0836. (doi:10.1038/nature06882) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1038/nature06882

Abstract

Metabolic phenotypes are the products of interactions among a variety of factors- dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H 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). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, 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. 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, 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.

Item Type: Article
DOI/Identification number: 10.1038/nature06882
Uncontrolled keywords: alanine, biological marker, formic acid, hippuric acid, biomarker, cardiovascular disease, diet, epidemiology, excretion, hominid, metabolite, microbial activity, multiple regression, nuclear magnetic resonance, phenotype, risk factor, adult, age distribution, article, blood pressure, cardiovascular risk, China, diet, disease association, epidemiological data, female, human, ischemic heart disease, Japan, major clinical study, male, microbial activity, multiple regression, nuclear magnetic resonance spectroscopy, pathogenesis, phenotype, phenotypic variation, principal component analysis, priority journal, protein intake, statistical significance, stroke, United Kingdom, United States, urinalysis, urinary excretion, vegetable, Adult, Alanine, Animals, Blood Pressure, Cardiovascular Diseases, China, Diet, Dietary Proteins, Female, Great Britain, Hippurates, Humans, Intestines, Japan, Magnetic Resonance Spectroscopy, Male, Metabolism, Middle Aged, Phenotype, Principal Component Analysis, Time Factors, United States, Vegetables, Asia, China, Eurasia, Europe, Far East, Japan, North America, United Kingdom, United States, Western Europe
Subjects: Q Science
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Rueyleng Loo
Date Deposited: 14 Nov 2013 22:15 UTC
Last Modified: 19 Jun 2019 11:31 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/36453 (The current URI for this page, for reference purposes)
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