Serum lncRNAs in early pregnancy as potential biomarkers for the prediction of pregnancy-induced hypertension, including preeclampsia

Abstract

Long noncoding RNAs (lncRNAs) are key mediators of biological regulation with diagnostic value as disease biomarkers. We explored serum lncRNA levels in early pregnancy as potential biomarkers of pregnancy-induced hypertension (PIH), including gestational hypertension (GH) and preeclampsia (PE). We performed a two-phase nested case-control study in pregnant women before 20 weeks’ gestation (before clinical diagnosis). The screening phase assessed lncRNA expression profiles with a human lncRNA microarray in 5 pairs of serum samples (5 PE patients and 5 matched controls). The second phase validated levels of 8 candidate lncRNAs selected via the random walk method by quantitative real-time polymerase chain reaction (qRT-PCR). Serum levels of the 8 lncRNAs were markedly increased in women with PIH compared with matched normotensive pregnant (NP) women (p < 0.001), consistent with the microarray results. In addition, 7 candidate lncRNAs were correlated with PIH severity. Logistic regression analysis revealed that serum levels of ENST00000527727 (odds ratio [OR], 1.113; 95% confidence interval [CI], 1.024–1.209; p = 0.0113) and ENST00000415029 (OR, 1.126; 95% CI, 1.000–1.267; p = 0.0496) were associated with adverse pregnancy outcomes, such as fetal growth restriction (FGR) and placenta accreta of PIH. Nine pathways associated with the candidate lncRNAs had confirmed associations with PIH.