[Microarray analysis of differentially expressed genes in peripheral leucocytes derived from severe preeclampsia and normotensive pregnancies].

OBJECTIVE

To investigate genes involved in the mechanisms underlying the progression of severe preeclampsia.

METHODS

We conducted a multiregional gene expression analysis using peripheral leucocytes from patients with preeclampsia and normal controls. Total RNA was extracted from peripheral blood of six severe preeclampsia and five normotensive pregnancies. We performed genome-wide expression profiling using Affymetrix HG_U133 plus 2.0 chips to screen out differentially expressed genes of 2 fold or more and q_value < 5.4%. Using Gene Ontology we identified the function of differentially expressed genes after cluster analysis.

RESULTS

Among the 47 000 genes that were screened in the microarray, 140 genes were found to be differentially expressed between normal and preeclamptic pregnancies. Eighty six up-regulated candidate genes were mainly involved in cysteine metabolism urea cycle and metabolism of amiogroups, proteasome, TGF-beta signaling pathway, and the ratio of calponin2 (CNN2), matrix metallopeptidase 8 (MMP8), V-set and immunoglobulin domain containing 4 (VSIG4), proteasome 26S subunit ATPase 5 (PSMC5) was evidently increased in preeclampsia patients. Among 54 down-regulated candidates, natural killer cell mediated cytotoxicity, antigen processing and presentation, metabolism of xenobiotics by cytochrome P450 were the main pathways. KIR3DL2, AKR1C3, CHURC1 and SLC25A13 were obviously decreased in preeclampsia patients.

CONCLUSIONS

The gene expression of peripheral leucocytes in preeclampsia patients is significantly different from that of uncomplicated pregnancies. CNN2, MMP8, VSIG4, PSMC5, KIR3DL2, AKR1C3, CHURC1 and SLC25A13 may be involved in the molecular mechanisms underlying the progression of severe preeclampsia.