184: Pre-eclampsia, diabetes, and the placenta: a study in differential gene expression & molecular clues to disease states


      While the exact etiology of pre-eclampsia remains a mystery, the role of the placenta in the pathophysiology of pre-eclampsia continues to be implicated, making the placenta a prime candidate for examining genetic perturbations in gravidae with pre-eclampsia and commonly found co-morbidities such as diabetes.
      We previously investigated global placental gene expression among diabetic gravidae, by applying whole transcriptome RNA sequencing (RNA-Seq) and robust computational analysis and found novel changes in placental gene expression by virtue of maternal diabetic status. In this current study we examined a clinically relevant cohort of both diabetic and non diabetic gravidae with the aim of determining placental gene expression changes specific for frequently co-morbid, hypertensive disorders of pregnancies as compared to controls.

      Study Design

      Whole transcriptome sequencing was undertaken with extensively clinically phenotyped, population-based subject placental samples (n=29) on the HiSeq (Illumina), rendering over 150 million reads/sample. RNA Seq computational analysis was used to identify significant placental gene expression differences among our cohort. Two independent, computational platforms (edgeR and DESeq2) were used to verify differential gene expression.


      Significant placental gene expression differences were noted in the gravidae with pre-eclampsia as compared to controls (FDR <0.05). Additionally, significant differential gene expression was noted in gravidae with diabetes (both GDM and Type II) and pre-eclampsia when compared to those that had neither, after controlling for subjects with only diabetes or pre-eclampsia (FDR<0.05). Summary data are projected as a heat map (Figure) where values are log2 transformed read counts that have been quantile normalized. Subsequent annotation following control for multiple comparisons revealed significant differences in 782 genes mapping to multiple pathways (p<10-6).


      Novel placental gene expression differences were seen when stratified by pre-eclampsia and diabetes status. This work in a large population-based cohort further emphasizes the synergistic nature of these conditions, and reveals underlying placental gene pathways which may drive maternal comorbidity.
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