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C1431T Variant of PPARγ Is Associated with Preeclampsia in Pregnant Women
Fulin Liu1, Christine Rouault2, Karine Clément2,3
1Pathophysiology & Pharmacotoxicology of the Human Placenta, Pre & Postnatal Microbiota, 3PHM, INSERM, Université de Paris, F-75006 Paris, France.
Insights
Peroxisome proliferator-activated receptor gamma (PPARγ) single nucleotide polymorphisms (SNPs) are linked to preeclampsia. A predictive model using PPARγ SNPs and clinical factors accurately identifies preeclampsia risk.
Area of Science:
- Genetics and Obstetrics
- Biomarkers for Pregnancy Complications
Background:
- Peroxisome proliferator-activated receptor gamma (PPARγ) is crucial for placental development.
- Single nucleotide polymorphisms (SNPs) in PPARγ are associated with increased susceptibility to pregnancy diseases like preeclampsia.
Purpose of the Study:
- To investigate the association between preeclampsia and three specific PPARγ SNPs (Pro12Ala, C1431T, C681G).
- To develop a pragmatic predictive model for preeclampsia using PPARγ SNPs and clinical factors.
Main Methods:
- Analysis of 1648 women (35 with preeclampsia) from the EDEN cohort.
- Univariate and multivariate feature selection to identify predictors.
- Machine learning algorithms (boost tree-based model) for predictive modeling.
- Performance evaluation using accuracy and Area Under the Curve (AUC).
Main Results:
- The PPARγ SNP C1431T was significantly associated with preeclampsia (p < 0.05, OR 4.90-8.75).
- Seven features, including PPARγ variants (C1431T, C681G) and clinical factors, were identified as potential predictors.
- The boost tree model achieved high accuracy (0.971 training, 0.951 testing) and AUC (0.991 training, 0.701 testing).
Conclusions:
- The PPARγ C1431T variant is significantly associated with preeclampsia susceptibility.
- A decision tree model integrating genetic and clinical factors can predict preeclampsia early in pregnancy.
Abstract:
Peroxisome proliferator-activated receptor γ (PPARγ) is essential for placental development, whose SNPs have shown increased susceptibility to pregnancy-related diseases, such as preeclampsia. Our aim was to investigate the association between preeclampsia and three PPARγ SNPs (Pro12Ala, C1431T, and C681G), which together with nine clinical factors were used to build a pragmatic model for preeclampsia prediction. Data were collected from 1648 women from the EDEN cohort, of which 35 women had preeclamptic pregnancies, and the remaining 1613 women had normal pregnancies. Univariate analysis comparing preeclamptic patients to the control resulted in the SNP C1431T being the only factor significantly associated with preeclampsia (p < 0.05), with a confidence interval of 95% and odds ratio ranging from 4.90 to 8.75. On the other hand, three methods of multivariate feature selection highlighted seven features that could be potential predictors of preeclampsia: maternal C1431T and C681G variants, obesity, body mass index, number of pregnancies, primiparity, cigarette use, and education. These seven features were further used as input into eight different machine-learning algorithms to create predictive models, whose performances were evaluated based on metrics of accuracy and the area under the receiver operating characteristic curve (AUC). The boost tree-based model performed the best, with respective accuracy and AUC values of 0.971 ± 0.002 and 0.991 ± 0.001 in the training set and 0.951 and 0.701 in the testing set. A flowchart based on the boost tree model was constructed to depict the procedure for preeclampsia prediction. This final decision tree showed that the C1431T variant of PPARγ is significantly associated with susceptibility to preeclampsia. We believe that this final decision tree could be applied in the clinical prediction of preeclampsia in the very early stages of pregnancy.
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