Abstract 623: Robust Strategy to Identify Metabolomic Markers of Preeclampsia
Background. Despite considerable progress in recent years the pathogenesis of preeclampsia remains incompletely understood. Metabolomic studies have the potential to discover novel disease pathways through an unbiased approach but are prone to exaggerating small but statistically significant differences in metabolite levels.
Methods. We selected 36 women who participated in the Proteomics in Preeclampsia (PIP) study from whom plasma samples at gestational weeks 16 and 28 were available. Of these, 18 subsequently developed preeclampsia (cases) and 18 had normotensive pregnancies (controls). Metabolomic studies were performed in plasma using hydrophilic interaction liquid chromatography coupled to Orbitrap high resolution mass spectrometry (HILIC-MS). Statistical analysis was performed using IDEOM version 13.0. More than 2-fold change and false discovery rate (FDR) < 0.05 were considered as statistically significant between the groups (i.e., cases and controls at each gestational age, and between different gestational ages within cases and controls separately).
Results. We detected 133 metabolites which were differentially expressed between the groups. We identified the amino sulfonic acid taurine as differentially regulated between cases and controls with 1.47 and 2.09-fold lower levels in cases compared to controls at weeks 16 and 28, respectively, and with a 1.42-fold increase from week 16 to 28 in controls as opposed to no change in cases. Significant increases (2.28 to 2.92-fold) in progesterone and related metabolites (pregnanediol-3-glucuronide and [ST (2:0)] 5 alpha-cholesta-8,24-dien-3beta-ol) during pregnancy in all women were expected and add further confidence to our data.
Conclusion. Our longitudinal study design and an analysis strategy based not only on statistical significance but also on fold changes detects taurine as marker of preeclampsia. Taurine has anti-inflammatory properties and reduced levels could provide a mechanistic explanation for development of preeclampsia in some women.
- © 2012 by American Heart Association, Inc.