Comparison of normal and pre-eclamptic placental gene expression: A systematic review with meta-analysis

Abstract

Pre-eclampsia (PE) is a serious multi-factorial disorder of human pregnancy. It is associated with changes in the expression of placental genes. Recent transcription profiling of placental genes withmicroarray analyses have offered better opportunities to define the molecular pathology of this disorder. However, the extent to which placental gene expression changes in PE is not fully understood.We conducted a systematic review of published PE and normal pregnancy (NP) control placental RNA microarrays to describe the similarities and differences between NP and PE placental gene expression, and examined how these differences could contribute to themolecular pathology of the disease. A total of 167 microarray samples were available for meta-analysis. We found the expression pattern of one group of genes was the same in PE and NP. The review also identified a set of genes (PE unique genes) including a subset, that were significantly (p < 0.05) down-regulated in pre-eclamptic placentae only. Using class prediction analysis, we further identified the expression of 88 genes that were highly associated with PE (p < 0.05), 10 of which (LEP, HTRA4, SPAG4, LHB, TREM1, FSTL3, CGB, INHA, PROCR, and LTF) were significant at p < 0.001. Our review also suggested that about 30%of genes currently being investigated as possibly of importance in PE placenta were not consistently and significantly affected in the PE placentae.We recommend further work to confirm the roles of the PE unique and associated genes, currently not being investigated in themolecular pathology of the disease.