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

Yap, Ivan K. S., Brown, Ian J., Chan, Queenie, Wijeyesekera, Anisha, Garcia-Perez, Isabel, Bictash, Magda, Loo, Ruey Leng, Chadeau-Hyam, Marc, Ebbels, Timothy, de Lorio, Maria, and others. (2010) Metabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study. Journal of Proteome Research, 9 (12). pp. 6647-6654. ISSN 1535-3893. (doi:10.1021/pr100798r) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

Rates of heart disease and stroke vary markedly between north and south China. A 1H 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 &lt; 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. © 2010 American Chemical Society.

Item Type: Article
DOI/Identification number: 10.1021/pr100798r
Uncontrolled keywords: 2 hydroxyisobutyrate, 4 cresyl sulfate, aconitic acid, alanine, biological marker, creatine, dimethylglycine, glycoprotein, heptanoic acid derivative, hippuric acid, inositol, isoleucine, lactic acid, leucine, methylguanidine, n acetylneuraminic acid, phenylacetylglutamine, prolinebetaine, succinic acid, Tamm Horsfall glycoprotein, trace element, unclassified drug, valeric acid, valine, article, blood pressure, cardiovascular risk, Chinese, diet, false positive result, female, human, macronutrient, male, metabolite, metabolome, microbial metabolism, priority journal, proton nuclear magnetic resonance, urinalysis, Adult, 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, Mammalia
Subjects: Q Science
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Rueyleng Loo
Date Deposited: 14 Nov 2013 22:25 UTC
Last Modified: 29 May 2019 11:22 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/36450 (The current URI for this page, for reference purposes)
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