Abstract
BackgroundPreeclampsia (PE), as a multisystem disorder, is associated with maternal hypertension and proteinuria. Apoptosis seems to be involved in the pathophysiology of PE, although its precise pathogenic mechanisms are not well established. In this study, we aimed to identify the association between maternal TP53-rs1042522, P21-rs1801270, and P21-rs1059234 polymorphisms and PE. In addition, we examined the effects of promoter methylation and TP53 and P21 polymorphisms on placental mRNA expression in PE women.MethodsThe blood of 226 PE women and 228 normotensive pregnant women was examined in this study. In addition, the placentas were genotyped in 109 PE and 112 control women. The methylation status was assessed by a methylation-specific PCR assay, while mRNA expression was examined via Quantitative Real Time PCR.ResultsThe maternal and placental P21-rs1801270 CA genotype had a significant association with the reduced risk of PE. In the dominant, recessive, and allelic models, maternal/placental P21-rs1059234 polymorphism had no statistically significant association with the risk of PE. On the other hand, the reduced risk of PE was associated with maternal, but not placental TP53-rs1042522 polymorphism in the dominant and recessive models. The maternal and placental P21-rs1801270 polymorphism was associated with PE risk. The maternal P21 Trs1059234Crs1801270 haplotype was associated with 3.4-fold increase in PE risk, However the maternal P21 Trs1059234Ars 1801270 haplotype and placental Crs1059234CA rs1801270 haplotype led to 0.5 and 0.4-fold decrease in PE risk, respectively. PE women showed 5.6 times higher levels of placental mRNA expression of TP53 gene, although it was not associated with rs1042522 polymorphism. The relative placental mRNA expression of P21 gene was 0.2 in PE women. It was also 2.4 times higher in individuals with rs1801270CA genotype than those with AA genotype. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a 3.4-fold and 3-fold increase in PE risk, respectively. However, no association was found between P21 and TP53 mRNA expression and promoter methylation.ConclusionIn conclusion, P21-rs1801270 and TP53-rs1042522 polymorphisms were involved in reduced risk of PE. P21-rs1801270 was associated with decreased P21 mRNA expression. The hyper-methylation of P21 and TP53 genes in the promoter region was associated with a higher PE risk.
Highlights
Preeclampsia (PE), as a multisystem disorder, is associated with maternal hypertension and proteinuria
Proteinuria was defined as ≥0.3 g/24 h or ≥ + 1 protein on a urine dipstick after the 20th gestational week, and hypertension was described as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg on two or more assessments [21]
In conclusion, our results suggest that TP53 and P21 polymorphisms could affect the risk of PE
Summary
Preeclampsia (PE), as a multisystem disorder, is associated with maternal hypertension and proteinuria. We examined the effects of promoter methylation and TP53 and P21 polymorphisms on placental mRNA expression in PE women. Aberrant cell turnover occurs in PE pregnancies, leading to increased apoptosis in placental trophoblasts [6]. Placental hypoxia can be led to increased apoptosis in syncytiotrophoblast cells and necrosis [7]. P53 protein, as a major transcription factor, is involved in the regulation of cell apoptosis, growth arrest, and DNA repair under cell stress conditions. Downstream transcription of elements contributing to cell apoptosis and cycle arrest (e.g., p21) is promoted by increased level of p53 [8]. At codon 72, a G > C substitution characterizes the TP53 gene polymorphism (P72R, rs1042522), which is found in the transactivation domain of the p53 protein with possible effects on the protein activity [12]. Rs1059234 (C70T) is another P21 polymorphism, which is located downstream the stop codon in the 3′-untranslated region
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
