胎源性SERPINB5基因水平与子痫前期发病的相关性研究

Study on the relativity of placental SERPINB5 gene level and preeclampsia

目的:探讨子痫前期患者在临床症状出现之前血浆中胎源性非甲基化丝氨酸蛋白酶抑制剂B5(serpin peptidase inhibitor,clade B,member 5,SERPINB5)基因含量的变化及其与该病发生的相关性。方法:选取孕妇325例,分别在其孕7～12周、孕13～18周及孕19～24周抽取外周血,提取血浆游离DNA,采用Taqman探针结合甲基化特异性PCR(methylationspecific PCR,MSP)技术检测各模板DNA经亚硫酸氢盐修饰后非甲基化SERPINB5基因的含量,代表胎儿游离DNA水平,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观察组,从正常孕妇中随机选取30例列入对照组,回顾性分析两组孕妇血浆中非甲基化SERPINB5基因水平的差异。结果:325例孕妇中26例发展为子痫前期患者,妊娠7～12周血浆中非甲基化SERPINB5基因含量与对照组差异无统计学意义(P>0.05);妊娠13～18周实验组该基因平均含量为139.56copies/ml,正常妊娠组为101.04copies/ml,差异具有统计学意义(P<0.05);妊娠19～24周实验组该基因含量为对照组的2.06倍。结论:妊娠中期孕妇血浆中非甲基化SERPINB5基因水平的异常变化有望实现子痫前期的早期预测。

Objective： To investigate the placental un - methylated SERPINB5 gene level in maternal plasma of pre - eclamptic pregnancies without clinical symptoms, and to explore the relativity of the gene level and preeelampsia. Methods： Selected 325 pregnant women of the first trimester, free DNA of plasma samples were extracted at 7 - 12 gestational weeks, 13 - 18 gestational weeks and 19 -24 gestational weeks, respectively. The un - methylated SERPINB5 gene after bisulfite conversion was detected by methylation - specific PCR （MSP） and TaqMan probe, which representing free fetal DNA level. Blood pressure, proteinuria and clinical feature were monitored at the same time. Who subsequently developed preeelampsia were selected as observation group, 30 normal pregnant women were selected as control group, the levels of un - methylated SERPINB5 gene were analyzed in maternal plasma retrospectively. Results ： 26 subjects of 325 pregnant women developed preeclampsia. There was no statistically significant difference in the level of un - methylated specific SERPINB5 gene at 7 - 12 gestational weeks between the observation and control groups; at 13 - 18 gestational weeks, the mean concentrations of the gene were 139. 56 copies/ml in maternal plasma of pre -eelamptic pregnaneies, 101.04 copies/ml in the controls, the difference had statistical signif- icance; the SERPINB5 gene level was 2.06 - fold higher in observation group than in control group at 19 - 24 gestational weeks. Conclusion ： The abnormal changes of un - methylated SERPINB5 gene in maternal plasma in second trimester may be expected to a- chieve the early prediction of preeclampsia.