EBF1 Gene mRNA Levels in Maternal Blood and Spontaneous Preterm Birth

Genetic variants of six genes (EBF1, EEFSEC, AGTR2, WNT4, ADCY5, and RAP2C) have been linked recently to gestational duration and/or spontaneous preterm birth (sPTB). Our goal was to examine sPTB in relation to maternal blood mRNA levels of these genes. We used a public gene expression dataset (GSE59491) derived from maternal blood in trimesters 2 and 3 that included women with sPTB (n = 51) and term births (n = 106) matched for maternal age, race/ethnicity, pre-pregnancy body mass index, smoking during pregnancy, and parity. T tests were used to examine mRNA mean differences (sPTB vs term) within and across trimesters, and logistic regression models with mRNA quartiles were applied to assess associations between candidate gene mRNA levels and sPTB. Based on these analyses, one significant candidate gene was used in a Gene Set Enrichment Analysis (GSEA) to identify related gene sets. These gene sets were then compared with the ones previously linked to sPTB in the same samples. Our results indicated that among women in the lowest quartile of EBF1 mRNA in the 2nd or 3rd trimester, the odds ratio for sPTB was 2.86 (95%CI 1.08, 7.58) (p = 0.0349, false discovery rate (FDR) = 0.18) and 4.43 (95%CI 1.57, 12.50) (p = 0.0049, FDR = 0.06), respectively. No other candidate gene mRNAs were significantly associated with sPTB. In GSEA, 24 downregulated gene sets were correlated with 2nd trimester low EBF1 mRNA and part of previous sPTB-associated gene sets. In conclusion, mRNA levels of EBF1 in maternal blood may be useful in detecting increased risk of sPTB as early as 2nd trimester. The potential underlying mechanism might involve maternal-fetal immune and cell cycle/apoptosis pathways.