CAJ | 학술논문

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RA SSF1A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.
목적 연구자간전기환자재임신조、중기혈장중태원성RASSF1A기인적수평,탐토기재예측자간전기발생화발전중적작용.방법 선취잉부325명,분별재기잉7～12주、13～18주급19～24주채외주혈,제취유리DNA,채용갑기화민감적한제성매절소화법연합형광정량PCR기술검측혈장중초갑기화RA SSF1A기인적함량,동시감측잉부혈압、뇨단백치급림상표현,장최종발전위자간전기적잉부렬입자간전기조,종정상잉부중수궤선취30명렬입대조조,회고성분석량조잉부혈장중초갑기화RASSF1A기인수평적차이,병진일보분석자간전기림상분류、분형여해기인농도적관계.결과 (1)325명잉부중26례발전위자간전기환자,재임신13～18주자간전기조초갑기화RASSF1A기인평균함량위141.62고패수/mL,정상임신조위98.90고패수/mL,차이유통계학의의；임신19～24주자간전기조RASSF1A기인함량위대조조적2.03배.(2)재임신13～24주,중도자간전기초갑기화RASSF1A기인농도균고우경도자간전기,차이균유통계학의의(P＜0.05).여만발형중도자간전기조상비,재임신19～24주조발형중도자간전기조RASSF1A기인적농도승고(P＜0.05).결론 잉부혈장중초갑기화RASSF1A기인농도적이상변화가능발생재임신중기,대조기예측자간전기적발생급진전구유중요의의.
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 RASSF1A 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 RASSF1A 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-eclampsia than late-onset severe pre-eclampsia at 19-24gestational 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.