Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Apoptosis. 2019 Apr;24(3-4):301-311. doi: 10.1007/s10495-018-1501-8.
The current study examined the effects of BAX and BCL2 polymorphisms and methylation as well as mRNA expression on susceptibility to PE. After delivery, the placentas were collected from 92 women with PE, as well as 106 normotensive pregnant women. The BAX rs4645878 and BCL2 rs2279115 polymorphisms were genotyped by the PCR-RFLP method. Methylation-specific PCR (MSP) was used for analysis of promoter methylation. mRNA expression was assayed by Quantitative RT-PCR. In addition, in silico analysis was performed by bioinformatics tools. There was no relationship between PE and placental BAX rs4645878 and BCL2 rs2279115 polymorphisms. The groups were not significantly different regarding the promoter methylation of BAX gene. Nonetheless, the MM status of BCL2 promoter had a significantly higher frequency in the PE group and was associated with 2.7-fold higher risk of PE (OR = 2.7, 95% CI = 1.3-5.6; P = 0.01). The relative mRNA expression of BCL2 was decreased in the placentas of PE women (P < 0.0001). The expression of BAX gene was not significantly different between the two groups. There was no association between placental BAX rs4645878 and BCL2 rs2279115 polymorphisms and mRNA expression levels. In silico analysis indicated that BAX rs4645878 and BCL2 rs2279115 polymorphisms were located in the core recognition site of different transcription factors and these substitutions of wild allele resulted in the loss and/ or change of these binding sites and subsequently may alter BCL2 and BAX expression. This study showed that the BAX and BCL2 polymorphisms and BAX promoter methylation were not associated with PE risk. The BCL2 promoter methylation was associated with lower BCL2 expression and higher PE susceptibility.
本研究探讨了 BAX 和 BCL2 多态性及甲基化以及 mRNA 表达对 PE 易感性的影响。分娩后，从 92 名患有 PE 的妇女和 106 名正常妊娠妇女的胎盘收集 BAX rs4645878 和 BCL2 rs2279115 多态性。PCR-RFLP 方法用于检测 BAX rs4645878 和 BCL2 rs2279115 多态性。MSP 用于分析启动子甲基化。mRNA 表达通过定量 RT-PCR 进行检测。此外，还通过生物信息学工具进行了计算机分析。PE 与胎盘 BAX rs4645878 和 BCL2 rs2279115 多态性之间没有关系。两组在 BAX 基因启动子甲基化方面没有显著差异。然而，BCL2 启动子的 MM 状态在 PE 组中出现频率更高，与 PE 的 2.7 倍风险相关（OR=2.7，95%CI=1.3-5.6；P=0.01）。PE 妇女胎盘的 BCL2 相对 mRNA 表达降低（P<0.0001）。两组之间 BAX 基因的表达没有显著差异。胎盘 BAX rs4645878 和 BCL2 rs2279115 多态性与 mRNA 表达水平之间没有关联。计算机分析表明，BAX rs4645878 和 BCL2 rs2279115 多态性位于不同转录因子的核心识别位点，野生等位基因的这些替换导致这些结合位点的丢失和/或改变，随后可能改变 BCL2 和 BAX 的表达。本研究表明，BAX 和 BCL2 多态性和 BAX 启动子甲基化与 PE 风险无关。BCL2 启动子甲基化与 BCL2 表达降低和更高的 PE 易感性相关。
