妊娠中期妇女超甲基化RASSF1A基因表达水平与子痫前期的关系

Relationship between pre-eclampsia and maternal expression of the hypermethylated RASSF1A gene during the second trimester

目的 探讨妊娠中期妇女血浆中超甲基化RASSF1A基因表达水平变化与子痫前期的关系。方法 选择规律产前检查孕妇506例,分别于孕15-19周及孕20-24周采外周血,同时监测孕妇血压、尿蛋白值,其中诊断为妊娠期高血压疾病的孕妇中包括子痫前期组（48例）、妊娠期高血压组（48例）,从同期单胎健康孕妇中随机选取96名为对照组。收集入组孕妇外周血,提取游离DNA,经甲基化敏感的限制性内切酶消化处理,联合荧光定量PCR检测血浆中超甲基化RASSF1A基因的表达水平,分析其与子痫前期的关系。结果 孕15-19周,子痫前期组及妊娠期高血压组的超甲基化RASSF1A基因表达水平均高于对照组（P〈0.05）,子痫前期组与妊娠期高血压组组间比较差异无统计学意义（P〉0.05）。孕20-24周,子痫前期组孕妇血浆中超甲基化RASSF1A基因表达水平高于妊娠期高血压组及正常妊娠组（P〈0.05）,妊娠期高血压组孕妇血浆中超甲基化RASSF1A基因表达水平亦高于正常妊娠组（P〈0.05）。结论 妊娠中期妇女血浆中超甲基化RASSF1A基因水平升高可能提示子痫前期的发生。

Objective This study sought to investigate the relationship between pre-eclampsia and the expression of the hypermethylated RASSF1A gene in maternal plasma during the second trimester. Methods Peripheral blood samples were collected at 15 - 19 and 20 - 24 weeks of gestation from 506 pregnant women who received regular prenatal examinations. The blood pressures and urine protein levels of these women were monitored, and women who were diagnosed with gestational hypertension were divided into a pre-eclampsia group （48 subjects） and gestational hypertension group （48 subjects）. A total of 96 healthy women with singleton pregnancies during the same time period were included in the control group. Free DNA was extracted from peripheral blood samples from the included pregnant women and then digested with a methylation-sensitive restriction endonuclease. Plasma expression levels of the hypermethylated RASSF1A gene were determined using fluorescence quantitative polymerase chain reaction （PCR）, and the relationship between these levels and pre-eclampsia was analyzed. Results At 15 - 19 weeks of gestation, both the pre-eclampsia group and the gestational hypertension group exhibited higher hypermethylated RASSF1A expression than that of the control group （P 〈 0. 05 ）, whereas no significant differences between the pre-eclampsia group and the gestational hypertension group were observed （P 〉 0. 05 ）. At 20 - 24 weeks of gestation, plasma RASSF1A expression was higher in the pre-eclampsia group than in the gestational hypertension group or the control group （P 〈 0. 05 ）, and plasma RASSF1A expression was higher in the gestational hypertension group than in the control group （P 〈 0. 05）. Conclusion Elevated hypermethylated RASSF1A expression in maternal plasma during the second trimester may indicate the onset of pre-eclampsia.