孕妇外周血中高甲基化RASSF1A基因检测对子痫前期早期预测价值的研究
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摘要
目的通过分析子痫前期孕妇外周血中胎儿高甲基化RASSF1A基因含量的变化,探讨孕妇外周血中胎儿游离DNA水平在子痫前期中的预测诊断价值。方法收集子痫前期孕妇外周血样本32例,择同期孕龄健康孕妇30例为对照组,采用荧光定量PCR法检测孕妇外周血中高甲基化RASSF1A基因的含量,应用受试者工作特征曲线(ROC)评价高甲基化RASSF1A基因检测对轻度和重度子痫前期孕妇的诊断价值。结果轻度子痫前期组和重度子痫前期组孕妇血浆高甲基化RASSF1A基因的中位数倍值分别是正常妊娠孕妇的3.28倍和10.47倍,有统计学差异(P<0.01);用高甲基化的RASSF1A的1.71MoMs来预测轻度子痫前期,灵敏度为86.4%,特异度为71.2%。结论孕妇血浆中高甲基化的RASSF1A基因含量的变化可以提示子痫前期的发生及病情发展的监测,孕妇血浆胎儿游离DNA可作为一个早期预测孕妇子痫前期的发生的潜在的生物学指标。
Objective To explore the value of cell-free fetal DNA for predicting preeclampsia by analyzing the content of fetal hypermethylated RASSF1 Agene in maternal plasma in preeclampsia and different gestational age of normal pregnancy.Methods 32 cases of pregnant women with preeclampsia and 30 cases of normal pregnant women with the same gestational age were collected.Fetal hypermethlated RASSF1 Agene were detected by real-time PCR.And the optimal cut-off values of the fetal hypermethylated RASSF1 Agene for mild and severe pre-eclampsia were determined with receiver operating characteristic curve(ROC).Results The multiple of medians(MoMs)of hypermethylated RASSF1 Aconcentration in mild and severe PE group were significantly higher than those in the control group by about3.28 and 10.47 folds respectively(P<0.01).Using a cut-off value of 1.71 MoMs of hypermethylated RASSF1 Ato predict mild preeclampsia,the sensitivity was 86.4% and the specificity was 71.2%.Conclusion Hypermethylated RASSF1 Aconcentration in maternal plasma can be informative to predict the PE occurrence.Content of cell-free fetal DNA in maternal plasma could be a potential biomarker to predict preeclampsia at early stage.
Objective To explore the value of cell-free fetal DNA for predicting preeclampsia by analyzing the content of fetal hypermethylated RASSF1 Agene in maternal plasma in preeclampsia and different gestational age of normal pregnancy.Methods 32 cases of pregnant women with preeclampsia and 30 cases of normal pregnant women with the same gestational age were collected.Fetal hypermethlated RASSF1 Agene were detected by real-time PCR.And the optimal cut-off values of the fetal hypermethylated RASSF1 Agene for mild and severe pre-eclampsia were determined with receiver operating characteristic curve(ROC).Results The multiple of medians(MoMs)of hypermethylated RASSF1 Aconcentration in mild and severe PE group were significantly higher than those in the control group by about3.28 and 10.47 folds respectively(P<0.01).Using a cut-off value of 1.71 MoMs of hypermethylated RASSF1 Ato predict mild preeclampsia,the sensitivity was 86.4% and the specificity was 71.2%.Conclusion Hypermethylated RASSF1 Aconcentration in maternal plasma can be informative to predict the PE occurrence.Content of cell-free fetal DNA in maternal plasma could be a potential biomarker to predict preeclampsia at early stage.
引文
[1]Hee JP,Sung SS,Dong HC.Combined screening for early detection of Pre-eclampsia[J].Int J Mol Sci,2015,16:17952.
[2]Hyett J.Combined first trimester or cffDNA screening[J].BJOG,2016,123(1):98.
[3]Kim MJ,Kim SY,Park SY,et al.Association of fetal derived hypermethylated RASSF1A concentration in placenta mediated pregnancy complications[J].Placenta,2013,34:57.
[4]谢幸,苟文丽.妇产科学[M].第8版.北京:人民卫生出版社,2013:64-71.
[5]Francesca S,Annalisa I,Maddalena S,et al.Prospective evaluation of RASSF1Acell-free DNA as a Biomarker of Pre-eclampsia[J].Placenta,2015,36(9):996.
[6]冉贵萍,黄氲,杜金龙,等.妊娠各期母血中胎儿RASSF1A基因含量的测定[J].中国优生与遗传杂志,2018,26(1):13.
[7]Helen EW,Carolyn LD,Victoria JH,et al.Evaluation of a novel assay for detection of the fetal marker RASSF1A:facilitating improved diagnostic reliability of noninvasive prenatal diagnosis[J].PLoS One,2012,7(9):e45073.
[8]Angela NB,Li X,Tuan ZT,et al.Measurement of fetal fraction in cell-free DNA from maternal plasma using apanel of insertion/deletion polymorphisms[J].PLoS One,2017,2(10):e0186771.
[9]Xiongbin K,Jun X,Yicong W,et al.An Advanced model to precisely estimate the cell-Free fetal DNA concentration in maternal plasma[J].PLoS One,2016,11(9):e0161928.
[10]Saraswathy S,Sahai K,Yadav TP,et al.Evaluation of fetal hypermethylated RASSF1Ain pre-eclampsia and its relationship with placental protein-13,pregnancy associated plasma protein-Aand urine protein[J].Pregnancy Hypertens,2016,6(4):306.
[11]Yu H,Shen YT,Ge QY,et al.Quantification of maternal serum cell-Free fetal DNA in Early-Onset preeclampsia[J].Int J Mol Sci,2013,14:7571.
[12]Sifakis S,Zaravinos A,Maiz N,et al.First-trimester maternal plasma cell-free fetal DNA and preeclampsia[J].Am J Obstet Gynecol,2009,01:472e1.
[13]徐亚玲,常颖,陈叙.子痫前期预测指标的临床应用研究进展[J].国际妇产科学杂志,2016,43(1):11.
[2]Hyett J.Combined first trimester or cffDNA screening[J].BJOG,2016,123(1):98.
[3]Kim MJ,Kim SY,Park SY,et al.Association of fetal derived hypermethylated RASSF1A concentration in placenta mediated pregnancy complications[J].Placenta,2013,34:57.
[4]谢幸,苟文丽.妇产科学[M].第8版.北京:人民卫生出版社,2013:64-71.
[5]Francesca S,Annalisa I,Maddalena S,et al.Prospective evaluation of RASSF1Acell-free DNA as a Biomarker of Pre-eclampsia[J].Placenta,2015,36(9):996.
[6]冉贵萍,黄氲,杜金龙,等.妊娠各期母血中胎儿RASSF1A基因含量的测定[J].中国优生与遗传杂志,2018,26(1):13.
[7]Helen EW,Carolyn LD,Victoria JH,et al.Evaluation of a novel assay for detection of the fetal marker RASSF1A:facilitating improved diagnostic reliability of noninvasive prenatal diagnosis[J].PLoS One,2012,7(9):e45073.
[8]Angela NB,Li X,Tuan ZT,et al.Measurement of fetal fraction in cell-free DNA from maternal plasma using apanel of insertion/deletion polymorphisms[J].PLoS One,2017,2(10):e0186771.
[9]Xiongbin K,Jun X,Yicong W,et al.An Advanced model to precisely estimate the cell-Free fetal DNA concentration in maternal plasma[J].PLoS One,2016,11(9):e0161928.
[10]Saraswathy S,Sahai K,Yadav TP,et al.Evaluation of fetal hypermethylated RASSF1Ain pre-eclampsia and its relationship with placental protein-13,pregnancy associated plasma protein-Aand urine protein[J].Pregnancy Hypertens,2016,6(4):306.
[11]Yu H,Shen YT,Ge QY,et al.Quantification of maternal serum cell-Free fetal DNA in Early-Onset preeclampsia[J].Int J Mol Sci,2013,14:7571.
[12]Sifakis S,Zaravinos A,Maiz N,et al.First-trimester maternal plasma cell-free fetal DNA and preeclampsia[J].Am J Obstet Gynecol,2009,01:472e1.
[13]徐亚玲,常颖,陈叙.子痫前期预测指标的临床应用研究进展[J].国际妇产科学杂志,2016,43(1):11.