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Published on: June 29, 2013
First-Trimester Maternal Serum Growth Arrest-Specific Protein 6 (Gas6) Levels for the Prediction of Preeclampsia
Zehra Yılmaz1, Nazan Yurtcu2, Dilay Karademir2
1Department of Obstetrics and Gynecology, Private Practice, 55200 Samsun, Türkiye.
Insights
First-trimester serum Growth arrest-specific protein 6 (Gas6) levels are lower in preeclampsia (PE) cases. Lower Gas6 is particularly associated with early-onset PE, suggesting its potential as a predictive biomarker.
Area of Science:
- Reproductive Medicine
- Biomarker Discovery
- Maternal-Fetal Medicine
Background:
- Preeclampsia (PE) is a major cause of maternal and perinatal complications.
- Effective first-trimester biomarkers for PE prediction remain limited.
- Growth arrest-specific protein 6 (Gas6) plays a role in placental development.
Purpose of the Study:
- To investigate first-trimester serum Gas6 levels in women who develop PE.
- To assess the predictive value of Gas6 for different PE phenotypes.
- To evaluate Gas6 as a potential early biomarker for preeclampsia.
Main Methods:
- Prospective enrollment during first-trimester screening (11-14 weeks gestation).
- Nested case-control design with ELISA measurement of serum Gas6.
- Analysis included ROC curves and multivariate logistic regression.
Main Results:
- Serum Gas6 levels were significantly lower in PE cases compared to controls.
- Gas6 levels progressively decreased from controls to late-onset PE and early-onset PE.
- Gas6 demonstrated strong discriminatory power for early-onset PE (AUC=0.959).
Conclusions:
- First-trimester serum Gas6 is significantly reduced in preeclampsia, especially early-onset.
- Gas6 shows potential as a predictive biomarker for early-onset preeclampsia.
- Further validation is required before clinical application for screening.
Abstract:
Objective: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity; however, reliable first-trimester biomarkers are limited. Growth arrest-specific protein 6 (Gas6), a vitamin K-dependent ligand for the TAM receptor family (Tyro3, AXL, and MerTK), is crucial for trophoblast invasion and placental remodeling. This study evaluated whether first-trimester serum Gas6 levels differed between women with PE and controls and assessed the predictive utility across phenotypes. Methods: Participants were enrolled prospectively during routine first-trimester screening at 11 + 0 to 13 + 6 weeks, and cases and controls were selected using a nested case-control design after pregnancy outcomes were known. ROC-derived cut-off values for Gas6 were selected retrospectively using the Youden index and were considered exploratory. The PE group was divided into early (n = 15, <34 weeks) and late onset (n = 65, ≥34 weeks) subgroups. ELISA measured serum Gas6. Mann-Whitney U, Kruskal-Wallis, Spearman's correlation, ROC analysis, and multivariate logistic regression were applied. Results: Gas6 levels were significantly lower in PE than controls (15.73 vs. 38.08 ng/mL, p < 0.001); control reference median (38.08 ng/mL, IQR 27.62 to 49.14), decreasing progressively to late (20.07 ng/mL) and early onset PE (6.45 ng/mL; all p < 0.001). ROC analysis showed the highest exploratory discrimination for early onset preeclampsia (AUC = 0.959, 95% CI: 0.923-0.995; sensitivity 93.3%, specificity 84.1% at a retrospectively selected cut-off of ≤13.82 ng/mL), with more modest discrimination for overall PE (AUC = 0.762) and late onset PE (AUC = 0.708). Lower first-trimester Gas6 levels remained significantly associated with early onset PE after adjustment for maternal age and BMI (OR = 0.555, 95% CI: 0.412-0.748, p < 0.001). Conclusions: Serum Gas6 levels in the first trimester are lower in PE, particularly in cases of early onset disease, highlighting its potential as a candidate biomarker that requires further prospective and external validation before any screening application can be considered.
