Abstract
Objectives Preeclampsia (PE) is a common and serious pregnancy disorder with a strong genetic component. Numerous genetic studies performed, including our own, have yielded many susceptibility genes from distinct functional groups. Additionally, transcriptome profiling at the maternal-fetal interface has likewise yielded many differentially expressed genes. Often there is little overlap between the two approaches, although both are significantly informative with respect to PE. We have thus taken a novel approach by analysing pathways common to the susceptibility genes and the PE transcriptome. Methods Using Illumina Human Ht12v4 and Wg6v3 BeadChips, transcriptome profiling was conducted on n = 65 normotensive and n = 60 PE decidua basalis tissues collected at delivery. R software was used to pre-process transcript data for pathway analysis. Pathways were analysed and constructed using Ariadne Pathway Studio 9. We examined the following susceptibility genes: ACVR1, ACVR1C, ACVR2A, COL4A1, COL4A2, ERAP1, ERAP2, INHA, INHBB and LNPEP (Yong et al., 2014). Significance was set at p Results Major common targets/regulators of these susceptibility genes were AGT, IFNG, IL6, INHBA, SERPINE1, TGFB1 and VEGFA (Fig. 1). The top downstream pathway categories of susceptibility genes that were significantly altered in the PE decidual transcriptome were apoptosis and cell signalling. Conclusions Susceptibility genes from distinct functional groups have similar downstream pathways through common targets/regulators. Several of these pathways matched those altered in PE. This study contributes to a better understanding on how susceptibility genes may interact in the development of PE. With this knowledge, more targeted functional analyses of PE susceptibility genes in these key pathways can be performed to examine their contributions to the pathogenesis and severity of PE. Disclosures H.E. Yong: None. P.E. Melton: None. M.P. Johnson: None. K.A. Freed: None. B. Kalionis: None. P. Murthi: None. S.P. Brennecke: None. R.J. Keogh: None. E.K. Moses: None.
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More From: Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health
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