Relationship between plasma TRAIL before 20 weeks' gestation and pregnancy induced hypertension

Abstract

Objective To assess the relationship between maternal plasma tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) before 20 weeks' gestation and hypertensive disorder complicating pregnancy (HDCP); and to evaluate the predictive value of plasma TRAIL for HDCP. Methods A 2-phase screening/validation study was designed.In the screening phase, a nested, case-controlled study was performed, the plasma samples collected before 20 weeks' gestation from 20 women who later developed HDCP and 20 age-and gestation week-matched controls were tested in prospective screening test for protein expression profiling during pregnancy and HDCP. Plasma samples were analyzed by a human protein microarray technology designed to detect 507 proteins simultaneously. Differently expressed proteins' functional annotation and clustering were performed by using of Database for Annotation, Visualization and Integrated Discovery (DAVID) and Gene Ontology (GO) database. The TRAIL level of plasma samples obtained before 20 weeks' gestation from 53 women who later developed HDCP and 106 similarly matched controls were further validated by ELISA and 62 clinical risk factors were investigated. Logistic regression and ROC analysis were used to evaluate the relationship between TRAIL and HDCP and its predictive value for HDCP. Results In protein microarray analysis, 23 proteins expressed differently before 20 weeks' gestation between the two groups. Further validation results showed that TRAIL levels in HDCP patients were lower significantly (45.7±13.1) pg/ml than those in healthy pregnant controls(51.2±14.7)pg/ml, P=0.021. Multiple factor logistic regression analysis of 159 pregnancies showed that three features were finally entering the logistic model, they were: anemia (OR=4.87, 95% CI 1.05-24.26), pre-pregnancy BMI (OR=1.72, 95% CI 1.35-2.19) and TRAIL (OR=0.96, 95% CI 0.92-0.99). The predictive accuracy of logistic model was 81.8%. The model significantly increases the predictive value (AUC=0.81, 95% CI 0.73-0.87) compared to TRAIL as independent predictor (AUC=0.59, 95% CI 0.51-0.67). Conclusions Totally 23 proteins were expressed differentially before 20 weeks' gestation in plasma of women who later developed HDCP, confirming that HDCP is a heterogeneous disease with different biological changes. The data suggests that plasma TRAIL levels relate with the development of HDCP and its combination with pre-pregnancy BMI and anemia have a high predictive value for HDCP before 20 weeks' gestation.(Chin J Lab Med, 2015, 38: 522-527) Key words: Hypertension, pregnancy-induced; Receptors, TNF-related apoptosis-inducing ligand; Protein array analysis