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

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.

journal_name

Nature

journal_title

Nature

authors

Holmes E,Loo RL,Stamler J,Bictash M,Yap IK,Chan Q,Ebbels T,De Iorio M,Brown IJ,Veselkov KA,Daviglus ML,Kesteloot H,Ueshima H,Zhao L,Nicholson JK,Elliott P

doi

10.1038/nature06882

subject

Has Abstract

pub_date

2008-05-15 00:00:00

pages

396-400

issue

7193

eissn

0028-0836

issn

1476-4687

pii

nature06882

journal_volume

453

pub_type

杂志文章

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