Metabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study.

TitleMetabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study.
Publication TypeJournal Article
Year of Publication2010
AuthorsYap IKS, Brown IJ, Chan Q, Wijeyesekera A, Garcia-Perez I, Bictash M, Loo R L, Chadeau-Hyam M, Ebbels T, De Iorio M, Maibaum E, Zhao L, Kesteloot H, Daviglus ML, Stamler J, Nicholson JK, Elliott P, Holmes E
JournalJ Proteome Res
Volume9
Issue12
Pagination6647-54
Date Published2010 Dec 3
ISSN1535-3907
KeywordsAdult, Amino Acids, Branched-Chain, Asian Continental Ancestry Group, Biological Markers, Cardiovascular Diseases, China, Creatine, Discriminant Analysis, Female, Geography, Humans, Least-Squares Analysis, Magnetic Resonance Spectroscopy, Male, Metabolomics, Middle Aged, N-Acetylneuraminic Acid, Risk Assessment, Risk Factors, Succinic Acid, Uromodulin
Abstract

Rates of heart disease and stroke vary markedly between north and south China. A (1)H NMR spectroscopy-based metabolome-wide association approach was used to identify urinary metabolites that discriminate between southern and northern Chinese population samples, to investigate population biomarkers that might relate to the difference in cardiovascular disease risk. NMR spectra were acquired from two 24-h urine specimens per person for 523 northern and 244 southern Chinese participants in the INTERMAP Study of macro/micronutrients and blood pressure. Discriminating metabolites were identified using orthogonal partial least squares discriminant analysis and assessed for statistical significance with conservative family wise error rate < 0.01 to minimize false positive findings. Urinary metabolites significantly (P < 1.2 × 10(-16) to 2.9 × 10(-69)) higher in northern than southern Chinese populations included dimethylglycine, alanine, lactate, branched-chain amino acids (isoleucine, leucine, valine), N-acetyls of glycoprotein fragments (including uromodulin), N-acetyl neuraminic acid, pentanoic/heptanoic acid, and methylguanidine; metabolites significantly (P < 1.1 × 10(-12) to 2 × 10(-127)) higher in the south were gut microbial cometabolites (hippurate, 4-cresyl sulfate, phenylacetylglutamine, 2-hydroxyisobutyrate), succinate, creatine, scyllo-inositol, prolinebetaine, and trans-aconitate. These findings indicate the importance of environmental influences (e.g., diet), endogenous metabolism, and mammalian-gut microbial cometabolism, which may help explain north-south China differences in cardiovascular disease risk.

DOI10.1021/pr100798r
Alternate JournalJ. Proteome Res.
PubMed ID20853909
PubMed Central IDPMC3117148
Grant ListG0801056 / / Medical Research Council / United Kingdom
R01 HL050490 / HL / NHLBI NIH HHS / United States
R01 HL050490-17 / HL / NHLBI NIH HHS / United States
R01 HL084228 / HL / NHLBI NIH HHS / United States
R01 HL084228-04 / HL / NHLBI NIH HHS / United States
R01-HL050490 / HL / NHLBI NIH HHS / United States
R01-HL084228 / HL / NHLBI NIH HHS / United States