Skip to main content

Advertisement

SpringerLink
Log in

Detection and Identification of Novel Metabolomic Biomarkers in Preeclampsia

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

In a previous study, the ability of gas chromatography time-of-flight mass spectrometry to detect potential metabolic biomarkers in preeclampsia was demonstrated. In this study, the authors sought to validate their preliminary findings in an entirely different patient cohort using a complementary, novel, and powerful combination of analytical tools (ultra performance liquid chromatography and LTQ Orbitrap mass spectrometry system). Eight metabolites that appeared in the authors’ previous patient cohort were identified as being statistically significant (P < .01) as discriminatory biomarkers. The chemical identities of these 8 metabolites were established using authentic chemical standards. They included uric acid, 2-oxoglutarate, glutamate, and alanine. This is the first study to identify, in an unbiased manner, a series of small-molecular-weight metabolites that effectively detect preeclampsia in plasma. The identity of these metabolites provides new insights into the pathology of this condition and raises the possibility of the development of a predictive test.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI). Fifth Annual Report. Maternal and Child Health Research Consortium; 1998.

  2. Barker DJ, Gluckman PD, Godfrey KM, et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993;341:938–941.

    Article  CAS  Google Scholar 

  3. Hayman R, Brockelsby J, Kenny L, Baker P. Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial growth factor. J Soc Gynecol Investig. 1999;6:3–10.

    Article  CAS  Google Scholar 

  4. Pijnenborg R, Anthony J, Davey DA, et al. Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol. 1991;98:648–655.

    Article  CAS  Google Scholar 

  5. Kenny LC, Baker PN, Kendall DA, Randall MD, Dunn WR. Differential mechanisms of endothelium-dependent vasodilator responses in human myometrial small arteries in normal pregnancy and pre-eclampsia. Clin Sci (Lond). 2002;103:67–73.

    Article  CAS  Google Scholar 

  6. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989;161:1200–1204.

    Article  CAS  Google Scholar 

  7. Rodgers GM, Taylor RN, Roberts JM. Preeclampsia is associated with a serum factor cytotoxic to human endothelial cells. Am J Obstet Gynecol. 1988;159:908–914.

    Article  CAS  Google Scholar 

  8. Kell DB. Systems biology, metabolic modelling and metabolomics in drug discovery and development. Drug Discov Today. 2006;11:1085–1092.

    Article  CAS  Google Scholar 

  9. Raamsdonk LM, Teusink B, Broadhurst D, et al. A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations. Nat Biotechnol. 2001;19:45–50.

    Article  CAS  Google Scholar 

  10. Kenny LC, Dunn WB, Ellis DI, et al. Novel biomarkers for pre-eclampsia detected using metabolomics and machine learning. Metabolomics. 2005;1:227–234.

    Article  Google Scholar 

  11. Broadhurst D, Kell DB. Statistical strategies for avoiding false discoveries in metabolomics and related experiments. Metabolomics. 2006;2:171–196.

    Article  CAS  Google Scholar 

  12. Davey DA, MacGillivray I. The classification and definition of the hypertensive disorders of pregnancy. In: Hypertension in Pregnancy: the Proceedings of the 16th Study Group of the Royal College of Obstetricians and Gynaecologists. London, UK: RCOG; 1986:401–407.

    Google Scholar 

  13. Gopec Consortium. Disentangling fetal and maternal susceptibility for pre-eclampsia: a British multicenter candidate-gene study. Am J Hum Genet. 2005;77:127–131.

    Article  Google Scholar 

  14. Hu Q, Noll RJ, Li H, Makarov A, Hardman M, Graham Cooks R. The Orbitrap: a new mass spectrometer. J Mass Spectrom. 2005;40:430–443.

    Article  CAS  Google Scholar 

  15. Makarov A, Denisov E, Kholomeev A, et al. Performance evaluation of a hybrid linear ion trap/Orbitrap mass spectrometer. Anal Chem. 2006;78:2113–2120.

    Article  CAS  Google Scholar 

  16. Kind T, Fiehn O. Seven golden rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry. BMC Bioinformatics. 2007;8:105.

    Article  Google Scholar 

  17. Friedrich T, Roth M, Helm-Kruse S, Jeltsch A. Functional mapping of the EcoRV DNA methyltransferase by random mutagenesis and screening for catalytically inactive mutants. Biol Chem. 1998;379:475–480.

    Article  CAS  Google Scholar 

  18. Hollander M, Wolfe DA. Nonparametric Statistical Methods. New York, NY: Wiley; 1973.

    Google Scholar 

  19. Kell DB, Oliver SG. Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era. Bioessays. 2004;26:99–105.

    Article  Google Scholar 

  20. Redman CW, Bonnar J. Plasma urate changes in pre-eclampsia. BMJ. 1978;1:1484–1485.

    Article  CAS  Google Scholar 

  21. Dunn WB, Broadhurst DI, Sasalu D, et al. Serum metabolomics reveals many novel metabolic markers of heart failure, including pseudouridine and 2-oxoglutarate. Metabolomics. In press.

  22. Sabatine MS, Liu E, Morrow DA, et al. Metabolomic identification of novel biomarkers of myocardial ischemia. Circulation. 2005;112:3868–3875.

    Article  CAS  Google Scholar 

  23. Borzychowski AM, Sargent IL, Redman CW. Inflammation and pre-eclampsia. Semin Fetal Neonatal Med. 2006;11:309–316.

    Article  CAS  Google Scholar 

  24. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222:222–235.

    Article  CAS  Google Scholar 

  25. Redman CW, Sargent IL. Placental debris, oxidative stress and pre-eclampsia. Placenta. 2000;21:597–602.

    Article  CAS  Google Scholar 

  26. Redman CW, Sargent IL. Pre-eclampsia, the placenta and the maternal systemic inflammatory response-a review. Placenta. 2003;24(suppl A):S21–S27.

    Article  Google Scholar 

  27. Sargent IL, Borzychowski AM, Redman CW. NK cells and human pregnancy-an inflammatory view. Trends Immunol. 2006;27:399–404.

    Article  CAS  Google Scholar 

  28. Sharma JB, Sharma A, Bahadur A, Vimala N, Satyam A, Mittal S. Oxidative stress markers and antioxidant levels in normal pregnancy and pre-eclampsia. Int J Gynecol Obstet. 2006;94: 23–27.

    Article  CAS  Google Scholar 

  29. Duarte NC, Becker SA, Jamshidi N, et al. Global reconstruction of the human metabolic network based on genomic and bibliomic data. Proc Natl Acad Sci USA. 2007;104:1777–1782.

    Article  CAS  Google Scholar 

  30. Kell DB. Metabolomics, machine learning and modelling: towards an understanding of the language of cells. Biochem Soc Trans. 2005;33:520–524.

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. DB, MB, and WBD contributed equally to this work.

Authors and Affiliations

  1. Maternal and Fetal Health Research Centre, University of Manchester, St Mary’s Hospital, Manchester, UK

    Louise C. Kenny MBChB (Hons), PhD, MRCOG & Philip N. Baker DM, FRCOG

  2. Department of Obstetrics and Gynaecology, University College Cork, Cork University Maternity Hospital, Wilton, Cork, Ireland

    Louise C. Kenny MBChB (Hons), PhD, MRCOG & Douglas B. Kell BA (Hons), MA, DPhil

  3. School of Chemistry and the Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK

    David Broadhurst PhD, Marie Brown PhD, Warwick B. Dunn PhD & Douglas B. Kell BA (Hons), MA, DPhil

  4. Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Oxford, UK

    Christopher W. G. Redman MBBChir, MA, FRCP, FRCOG

  5. School of Medicine and the Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK

    Philip N. Baker DM, FRCOG

Authors
  1. Louise C. Kenny MBChB (Hons), PhD, MRCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Broadhurst PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marie Brown PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Warwick B. Dunn PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christopher W. G. Redman MBBChir, MA, FRCP, FRCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Douglas B. Kell BA (Hons), MA, DPhil
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Philip N. Baker DM, FRCOG
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Louise C. Kenny MBChB (Hons), PhD, MRCOG.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kenny, L.C., Broadhurst, D., Brown, M. et al. Detection and Identification of Novel Metabolomic Biomarkers in Preeclampsia. Reprod. Sci. 15, 591–597 (2008). https://doi.org/10.1177/1933719108316908

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719108316908

Key words

Search

Navigation