title: 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.
authors.affiliation: Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics (SORA), Faculty of Medicine, Imperial College London, South Kensington Campus, London SW7 2AZ, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Ruey Leng
authors.initials: RL
authors.lastname: Loo
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stamler
authors.forename: Magda
authors.initials: M
authors.lastname: Bictash
authors.forename: Ivan K S
authors.initials: IK
authors.lastname: Yap
authors.forename: Queenie
authors.initials: Q
authors.lastname: Chan
authors.forename: Tim
authors.initials: T
authors.lastname: Ebbels
authors.forename: Maria
authors.initials: M
authors.lastname: De Iorio
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Brown
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Veselkov
authors.forename: Martha L
authors.initials: ML
authors.lastname: Daviglus
authors.forename: Hugo
authors.initials: H
authors.lastname: Kesteloot
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Ueshima
authors.forename: Liancheng
authors.initials: L
authors.lastname: Zhao
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
mesh_terms: D000328:Adult; D000409:Alanine / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000378:metabolism; D002681:China; D004032:Diet; D004044:Dietary Proteins / Q000494:pharmacology; D005260:Female; D006626:Hippurates / Q000652:urine; D006801:Humans; D007422:Intestines / Q000382:microbiology; D007564:Japan; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008660:Metabolism / Q000502:physiology*; D008875:Middle Aged; D010641:Phenotype; D025341:Principal Component Analysis; D013997:Time Factors; D006113:United Kingdom; D014481:United States; D014675:Vegetables / Q000737:chemistry
chemical_list: D004044:Dietary Proteins; D006626:Hippurates; D000409:Alanine; C030514:hippuric acid