Genetic of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Biology, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran.
J Biomed Sci. 2019 Nov 8;26(1):92. doi: 10.1186/s12929-019-0586-x.
Preeclampsia (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.
The 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.
The 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 TC haplotype was associated with 3.4-fold increase in PE risk, However the maternal P21 TA haplotype and placental CA 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.
In 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.
子痫前期（PE）是一种多系统疾病，与母体高血压和蛋白尿有关。细胞凋亡似乎参与了 PE 的病理生理学过程，尽管其确切的发病机制尚未完全确定。在这项研究中，我们旨在确定母体 TP53-rs1042522、P21-rs1801270 和 P21-rs1059234 多态性与 PE 之间的关联。此外，我们还研究了启动子甲基化以及 TP53 和 P21 多态性对 PE 妇女胎盘 mRNA 表达的影响。
本研究检查了 226 名 PE 妇女和 228 名正常妊娠妇女的血液。此外，在 109 名 PE 妇女和 112 名对照妇女中对胎盘进行了基因分型。通过甲基化特异性 PCR 检测评估甲基化状态，通过定量实时 PCR 检测 mRNA 表达。
母体和胎盘 P21-rs1801270 CA 基因型与 PE 风险降低显著相关。在显性、隐性和等位基因模型中，母体/胎盘 P21-rs1059234 多态性与 PE 风险无统计学显著关联。另一方面，在显性和隐性模型中，PE 与母体而非胎盘 TP53-rs1042522 多态性相关。母体和胎盘 P21-rs1801270 多态性与 PE 风险相关。母体 P21 TC 单倍型与 PE 风险增加 3.4 倍相关，而母体 P21 TA 单倍型和胎盘 CA 单倍型导致 PE 风险分别降低 0.5 和 0.4 倍。PE 妇女的胎盘 TP53 基因 mRNA 表达水平高 5.6 倍，尽管与 rs1042522 多态性无关。PE 妇女的 P21 基因相对胎盘 mRNA 表达为 0.2。与 AA 基因型个体相比，rs1801270CA 基因型个体的 P21 基因 mRNA 表达高 2.4 倍。启动子区域 P21 和 TP53 基因的高甲基化与 PE 风险分别增加 3.4 倍和 3 倍相关。然而，在 P21 和 TP53 mRNA 表达与启动子甲基化之间未发现关联。
总之，P21-rs1801270 和 TP53-rs1042522 多态性与 PE 风险降低有关。P21-rs1801270 与 P21 mRNA 表达降低有关。启动子区域 P21 和 TP53 基因的高甲基化与较高的 PE 风险相关。
