子痫前期和复发性流产中差异的全球和 MTHFR 基因特异性甲基化模式：来自印度北部的病例对照研究。
Differential global and MTHFR gene specific methylation patterns in preeclampsia and recurrent miscarriages: A case-control study from North India.
机构信息
Department of Anthropology, University of Delhi, Delhi, India.
Centre for Cellular and Molecular Biology, Hyderabad, India.
出版信息
Gene. 2019 Jul 1;704:68-73. doi: 10.1016/j.gene.2019.04.036. Epub 2019 Apr 12.
AIM
The purpose of the present study is to evaluate and understand the association of global and MTHFR gene specific methylation in preeclampsia and recurrent miscarriages in light of MTHFR C677T polymorphism.
METHODS
The subjects comprised of recurrent miscarriage cases, their gestation matched controls, preeclampsia cases and matched controls. A set of women at full term were also recruited. Fasting blood sample (~5 ml) was drawn from all the participants followed by DNA extraction, global DNA methylation and MTHFR gene specific methylation. MTHFR C677T polymorphism was analysed by PCR followed by RFLP.
RESULTS HIGHER
Global DNA methylation at maternal front (p = 0.04) and hypomethylation of MTHFR gene at fetal front (p = 0.001) might be a characteristic of preeclampsia. Recurrent miscarriage cases were having significantly (p = 0.002) hyper MTHFR gene specific methylation as compared to controls. Women carrying CT genotype were found to be having significantly (p = 0.001) higher global DNA methylation in PE cases and MTHFR gene specific methylation (p = 0.005) in RM cases. Intergenerational analysis revealed similar patterns of global DNA methylation and MTHFR gene specific methylation among both PE and RM cases at maternal and fetal fronts.
CONCLUSION
The study highlights the importance of global DNA methylation in Preeclampsia and MTHFR gene specific methylation in recurrent miscarriages. MTHFR C677T gene polymorphism in association with global and gene specific methylation seem to play a pivotal role in PE and RM respectively.
目的
本研究旨在评估和了解 MTHFR 基因特定甲基化与早发性子痫前期和复发性流产的关系，同时考虑 MTHFR C677T 多态性。
方法
研究对象包括复发性流产病例、与其孕龄匹配的对照组、早发性子痫前期病例及匹配的对照组。还招募了一组足月妇女。所有参与者均空腹抽取 5ml 左右血液，提取 DNA，进行全基因组 DNA 甲基化和 MTHFR 基因特异性甲基化分析。MTHFR C677T 多态性通过 PCR 后 RFLP 进行分析。
结果
母体前区全基因组 DNA 甲基化升高（p=0.04）和胎儿前区 MTHFR 基因低甲基化（p=0.001）可能是早发性子痫前期的特征。与对照组相比，复发性流产病例的 MTHFR 基因特异性甲基化明显升高（p=0.002）。携带 CT 基因型的妇女在早发性子痫前期病例中全基因组 DNA 甲基化显著升高（p=0.001），在复发性流产病例中 MTHFR 基因特异性甲基化（p=0.005）也显著升高。世代间分析显示，早发性子痫前期和复发性流产病例在母体和胎儿前区均存在全基因组 DNA 甲基化和 MTHFR 基因特异性甲基化的相似模式。
结论
该研究强调了全基因组 DNA 甲基化在早发性子痫前期中的重要性，以及 MTHFR 基因特异性甲基化在复发性流产中的重要性。MTHFR C677T 基因多态性与全基因组和基因特异性甲基化的关联似乎分别在早发性子痫前期和复发性流产中发挥关键作用。
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