Differences and similarities in the transcriptional profile of peripheral whole blood in early and late-onset preeclampsia: insights into the molecular basis of the phenotype of preeclampsia

Objective: Preeclampsia (PE) can be sub-divided into early- and late-onset phenotypes. The pathogenesis of these two phenotypes has not been elucidated. To gain insight into the mechanisms of disease, the transcriptional profiles of whole blood from women with early- and late-onset PE were examined. Methods: A cross-sectional study was conducted to include women with: i) early-onset PE (diagnosed prior to 34 weeks, n=25); ii) late-onset PE (after 34 weeks, n=47); and iii) uncomplicated pregnancy (n=61). Microarray analysis of mRNA expression in peripheral whole blood was undertaken using Affymetrix microarrays. Differential gene expression was evaluated using a moderated t -test (false discovery rate 1.5), adjusting for maternal white blood cell count and gestational age. Validation by real-time qRT-PCR was performed in a larger sample size [early PE (n=31), late PE (n=72) and controls (n=99)] in all differentially expressed genes. Gene ontology analysis and pathway analysis were performed. Results: i) 43 and 28 genes were differentially expressed in early- and late-onset PE compared to the control group, respectively; ii) qRT-PCR confirmed the microarray results for early and late-onset PE in 77% (33/43) and 71% (20/28) of genes, respectively; iii) 20 genes that are involved in coagulation ( SERPINI2 ), immune regulation ( VSIG4, CD24 ), developmental process ( H19 ) and inflammation ( S100A10 ) were differentially expressed in early-onset PE alone. In contrast, only seven genes that encoded proteins involved in innate immunity ( LTF, ELANE ) and cell-to-cell recognition in the nervous system ( CNTNAP3 ) were differentially expressed in late-onset PE alone. Thirteen genes that encode proteins involved in host defense ( DEFA4, BPI , CTSG, LCN2 ), tight junctions in blood-brain barrier ( EMP1 ) and liver regeneration ( ECT2 ) were differentially expressed in both early- and late-onset PE. Conclusion: Early- and late-onset PE are characterized by a common signature in the transcriptional profile of whole blood. A small set of genes were differentially regulated in early- and late-onset PE. Future studies of the biological function, expression timetable and protein expression of these genes may provide insight into the pathophysiology of PE.