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

Ivan K.S. Yap, Ian J. Brown, Queenie Chan, Anisha Wijeyesekera, Isabel Garcia-Perez, Magda Bictash, Ruey Leng Loo, Marc Chadeau-Hyam, Timothy Ebbels, Maria De Iorio, Elaine Maibaum, Liancheng Zhao, Hugo Kesteloot, Martha L. Daviglus, Jeremiah Stamler, Jeremy K. Nicholson, Paul Elliott, Elaine Holmes*

*Corresponding author for this work

Research output: Contribution to journalArticle

95 Scopus citations

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 < 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.

Original languageEnglish (US)
Pages (from-to)6647-6654
Number of pages8
JournalJournal of Proteome Research
Volume9
Issue number12
DOIs
StatePublished - Dec 3 2010

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Fingerprint Dive into the research topics of 'Metabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study'. Together they form a unique fingerprint.

  • Cite this

    Yap, I. K. S., Brown, I. J., Chan, Q., Wijeyesekera, A., Garcia-Perez, I., Bictash, M., Loo, R. L., Chadeau-Hyam, M., Ebbels, T., Iorio, M. D., Maibaum, E., Zhao, L., Kesteloot, H., Daviglus, M. L., Stamler, J., Nicholson, J. K., Elliott, P., & Holmes, E. (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), 6647-6654. https://doi.org/10.1021/pr100798r