母血中胎源RASSF1A基因的表达水平对于子痫前期的预测价值  

Predictive value of placenta-derived RASSF1A sequence expression in maternal plasma for pre-eclampsia

作　　者：王健[1] 杨晶[3] 武晓红[2] 穆雅琴[1] 李拴明[1] 崔克[1] 王喜英[1] 赵富玺[1] 

机构地区：[1]山西省大同大学免疫学研究所,037009 [2]山西省大同大学继续教育学院 [3]山西省大同市第五人民医院血液科

出　　处：《中华医学遗传学杂志》2014年第1期25-28,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金（81170621）;山西省科技厅攻关项目（20080311072）;山西大同大学校级青年科学研究项目（2012Q15）

摘　　要：目的研究子痫前期患者在妊娠早、中期血浆中胎源性RASSF1A基因的水平，探讨其在预测子痫前期发生和发展中的作用。方法选取孕妇325名，分别在其孕7～12周、13～18周及19-24周采外周血，提取游离DNA，采用甲基化敏感的限制性酶切消化法联合荧光定量PCR技术检测血浆中超甲基化RASSF1A基因的含量，同时监测孕妇血压、尿蛋白值及临床表现，将最终发展为子痫前期的孕妇列入子痫前期组，从正常孕妇中随机选取30名列入对照组，回顾性分析两组孕妇血浆中超甲基化RASSF1A基因水平的差异，并进一步分析子痫前期临床分类、分型与该基因浓度的关系。结果（1）325名孕妇中26例发展为子痫前期患者，在妊娠13～18周子痫前期组超甲基化RASSF1A基因平均含量为141．62拷贝数／mL，正常妊娠组为98．90拷贝数／mL，差异有统计学意义；妊娠19～24周子痫前期组RASSF1A基因含量为对照组的2．03倍。（2）在妊娠13～24周，重度子痫前期超甲基化RASSF1A基因浓度均高于轻度子痫前期，差异均有统计学意义（P〈0．05）。与晚发型重度子痫前期组相比，在妊娠19～24周早发型重度子痫前期组RASSF1A基因的浓度升高（P〈0．05）。结论孕妇血浆中超甲基化RASSF1A基因浓度的异常变化可能发生在妊娠中期，对早期预测子痫前期的发生及进展具有重要意义。Objective To investigate the expression of placenta-derived RASSF1A gene in maternal plasma during first and second trimesters, and to explore its value for the prediction of pre-eclampsia. Methods For 325 pregnant women of the first trimester, free DNA of plasma samples was extracted at 7-12, 13-18, and 19-24 gestational weeks, respectively. Methylation-sensitive restriction enzyme digestion followed by fluorescence quantitative PCR （MSRE＋PCR） was employed for analyzing the concentrations of hypermethylatedRASSF1A gene. Blood pressure, proteinuria and clinical feature were monitored at the same time. Those who had subsequently developed pre-eclampsia were selected as the pre-eclamptic group, 30 normal pregnant women were selected as the control group. Hypermethylated RASSF1A gene in maternal plasma was retrospectively analyzed. The relationship between clinical classification, type of pre-eclampsia and concentrations of the gene were further analyzed. Results Twenty-six out of the 325 pregnant women developed pre-eclampsia as their only complication. At 13-18 gestational weeks, the mean concentrations of fetus-specific RASSFIA sequences were 141.62 copies/mL in maternal plasma of pre-eclamptic pregnancies, which was significantly greater than that of the controls （98.90 copies/mL）. Fetus derived RASSF1A levels were 2.03 fold higher in pre-eclamptic subjects than controls at 19-24 gestational weeks. There was a significant difference in the level of hypermethylated RASSFIA gene between the mild and severe pre-eclamptic subjects at 13 24 gestational weeks （P〈0.05）. The concentrations of the sequences were significantly higher in early-onset severe pre-eelampsia than late-onset severe pre-eclampsia at 19-24 gestational weeks （P〈0.05）. Conclusion Altered expression of hypermethylated RASSF1A gene may be detected in maternal plasma during second trimester, which has important significance for early prediction of pre-eclampsia.

关 键 词：子痫前期 超甲基化RASSF1A 荧光定量PCR 非侵入性产前诊断 

分 类 号：R714.244[医药卫生—妇产科学]