C1431T Variant of PPARγ Is Associated with Preeclampsia in Pregnant Women

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.

The Influence of FAM13A and PPAR-γ2 Gene Polymorphisms on the Metabolic State of Postmenopausal Women

“…In this study, the analysis of selected genotypes showed that the co-existence of PPAR-γ2 C1431C polymorphism with FAM13A rs1903003 (TT) or rs7671167 (TT), or rs2869967 (CC), was related to higher values of BMI and WHR. Interestingly, variant C1431T of PPAR-γ2 has been associated with obesity [ 52 ], hypertension, and preeclampsia risk [ 65 ]. Conversely, the PPAR-γ2 T1431 variant has opposing associations with body mass [ 66 ].…”

The Role of Peroxisome Proliferator-Activated Receptors in Preeclampsia

“…On the contrary, Holdsworth-Carson et al showed that placental PPARγ mRNA and protein were significantly increased in placentae from women that delivered preterm with co-existing intrauterine growth restriction and preeclampsia [83], while Jia et al noted high PPARγ protein expression levels in preeclamptic placental tissues, with the rs201018 polymorphism in the PPARγ promoter region significantly correlating with the development of preeclampsia [96]. Liu et al showed that the C1431T variant of PPARγ significantly correlates with preeclamptic susceptibility [97]. In addition, Permadi et al exposed primary trophoblastic cells obtained from normal pregnancy to serum from normal pregnancy, early-onset, or late-onset preeclampsia, and highlighted that exposure to serum from only late-onset preeclampsia induced high PPARγ expression [98].…”

Polygenic Risk Score and Risk Factors for Preeclampsia and Gestational Hypertension

“…Furthermore, a number of gene candidate-based studies of preeclampsia were conducted, resulting in a list of genes associated with the risk [9]. Among the genes reported to be associated with preeclampsia are MTHFR (rs1801133), F5 (rs6025) [10], NOS3 [11], PPARγ [12], ERAP2 [13], STOX1, CORIN, EPHX1, INO80B [14], GSTP1 [15], FGF5 [16], a role for the X chromosome [17] and several other chromosomal regions. According to this set of studies, some genes were found to affect susceptibility to preeclampsia in specific populations [18,19].…”