MON-LB094 Matrix Metalloproteinases Are Linked with Preeclampsia and May Be Useful as a Biomarker in Gestational Subclinical Hypothyroidism

Abstract

Gestational hypothyroidism has 5.1% prevalence and is associated with severe consequences as hypertensive complications and preeclampsia (PE). Based on the higher mortality associated with PE, the objective of this study is to identify new biomarkers useful as prognostic and therapeutically parameters. Methodology: The study was approved by the IRB Number: 665331/679727. We selected three volunteers to each group and constructed libraries of circulating RNA, for healthy pregnant women (HPW), preeclampsia (PEC) and gestational hypothyroidism (GHT). We collected blood samples for TSH and Free T4 (FT4) measurement and a PAX Gene Tube for RNA analysis. RNA extraction was performed by the PAXgene Blood RNA extraction kit (Qiagen NL, DE). NGS platform, Ion Proton System was used with Ion AmpliSeq Gene human transcriptome (Thermo Fisher Scientific Manufacturer) kit to construct the transcriptome libraries. The R software platform version 3.4.1 (R Foundation for Statistical Computing, Vienna, Austria. URL: R-project.org/) with the edgeR package 3.16.5 were used to determine the differentially expressed genes (DEG). We compared our GHT DEG with plasma transcriptome libraries from healthy pregnant women in the second and third trimesters (access number: GSE56899) available in GEO Dataset (ncbi.nlm.nih.gov/geo) using the limma package 3.26.8, p <0,05. We also used Random Forest (RF) analysis to rank the variables, Spearman Correlation, and multiclass ROC. Results: We encountered 713 DEG in the HPW with matrix metalloproteinases (MMP) upregulated, MMP8 (logFC 4.91) and MMP9 (logFC 3.44). In GEO Dataset we also found the MMP8 upregulated. We detected 195 DEG in PEC with MMP9 downregulated (logFC -2.49) and 745 DEG in GHT with MMP8 (logFC -4.06) and MMP9 (logFC -3.26) downregulated. We obtained 571 DEG in the analysis obtained by GEO Dataset and 26 genes are in common with our GHT DEG, including the MMP8. Between the 26 in common, 88.46% of genes were downregulated in GHT and 92.30% were upregulated GEO Dataset. We found a negative correlation of MMP8 with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r: -0.313; r: -0.285), MMP9 with SBP and DBP (r: -0.349; r: -0.384), MMP8 and MMP9 with weight (r: -0.223; r: -0.209) and MMP9 with TSH (r: 0.633). From our RF model, we selected the variables SBP and DBP, FT4 and weight that is possibly modified by the difference in expression of MMP8 and MMP9. We obtained an area under the curve of 0.97 for TSH, weight and those genes. Conclusion: Several metalloproteinases are involved in placental development, implantation and angiogenesis. We observed MMP8 and MMP9 downregulated in GHT. Although more studies are necessary, we found in the predictive model, TSH, weight and MMP8/MMP9 as the best combination to predict PE in GHT. Sources of Research Support: CNPq awarded to HD; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) awarded to CPC Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.