Gene expression profiling of maternal blood in early onset severe preeclampsia: identification of novel biomarkers

Abstract

To investigate candidate genes in peripheral blood mononuclear cell (PBMC) that are associated with early onset severe preeclampsia (ES-PE) and to describe candidate genes function using microarrays and real-time polymerase chain reaction (PCR). PBMC RNA was extracted from six patients with ES-PE and five uncomplicated pregnancies. The HG_U133 plus 2.0 Affymetrix GeneChips that represented 47,000 genes were used to measure gene expression in each sample. Significance analysis of microarray identified potential signature genes characterizing ES-PE vs. uncomplicated pregnancies. Eight genes were selected for confirmation by real-time PCR of 32 patients with ES-PE and 24 uncomplicated pregnancies, matched for maternal age, parity, race and gestational weeks. Using a whole-genome approach to study the molecular determinants of ES-PE, 72 genes were found to be differentially expressed between cases and controls, including 38 up-regulated genes and 34 down-regulated genes in the group of ES-PE. Killer cell immunoglobulin-like receptor, three domains, long cytoplasmic tail, 2 (KIR3DL2), aldo-keto reductase family 1, member C3 (AKR1C3), churchill domain containing 1 (CHURC1), and solute carrier family 25, member 13 (SLC25A13) were validated to be down-regulated in the patients with ES-PE by real-time PCR. Expression of genes with diverse function is associated with ES-PE risk, providing opportunities for the development of non-invasive diagnosis.