妊娠期高血压病患者血清DNMT1 mRNA和LncRNA UCA1水平表达与妊娠结局的关系

Relationship between the Expression of Serum DNMT1 mRNA and LncRNA UCA1 Levels and Pregnancy Outcome in Patients with Hypertensive Disorder Complicating Pregnancy

目的分析妊娠期高血压疾病(hypertensive disorder complicating pregnancy,HDCP)患者血清DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)信使RNA(messenger RNA,mRNA)、长链非编码RNA(long non-codingRNA,LncRNA)尿路上皮癌胚抗原1(urothelial carcinoembryonic antigen 1,UCA1)水平与妊娠结局的关系。方法选取2021年3月~2023年8月在邯郸市妇幼保健院诊治的HDCP患者195例为病例组、健康妊娠孕妇195例为对照组。收集所有孕妇临床资料并检测分娩前1天生化指标;荧光定量PCR法检测血清DNMT1 mRNA,LncRNA UCA1水平;根据病情将病例组分为妊娠期高血压(pregnancy induced hypertension,PIH)组、轻度子痫前期(preeclampsia,PE)组、重度PE组;根据HDCP患者分娩时不良妊娠结局情况分为妊娠结局良好组和妊娠结局不良组;比较对照组和病例组临床资料和生化指标、血清DNMT1 mRNA,LncRNA UCA1水平;比较不同严重程度HDCP患者血清DNMT1mRNA和LncRNA UCA1水平;比较不同妊娠结局HDCP患者临床资料和生化指标、血清DNMT1 mRNA和LncRNAUCA1水平;分析HDCP患者血清DNMT1 mRNA与LncRNA UCA1的相关性,影响HDCP患者妊娠结局的因素,血清DNMT1 mRNA和LncRNA UCA1对HDCP患者发生不良妊娠结局的预测价值。结果与对照组比较,病例组收缩压、舒张压、白细胞计数水平明显升高,血清DNMT1 mRNA(0.72±0.18 vs 1.00±0.04),LncRNA UCA1(0.61±0.16vs 1.00±0.02)水平明显降低,差异具有统计学意义(t=40.651,32.595,7.837,21.205,33.775,均P<0.001);PIH组、轻度PE组、重度PE组血清DNMT1 mRNA(0.85±0.20,0.74±0.18,0.50±0.15),LncRNA UCA1(0.77±0.18,0.58±0.16,0.43±0.13)水平依次降低,差异具有统计学意义(F=52.687,64.030,均P<0.001);HDCP患者血清DNMT1 mRNA与LncRNA UCA1呈正相关(r=0.582,P<0.001);与妊娠结局良好组比较,妊娠结局不良组HDCP严重程度较高,收缩压、舒张压、白细胞计数水平明显升高,血清DNMT1 mRNA(0.80±0.20 vs 0.59±0.15),LncRNA UCA1(0.72±0.17 vs 0.43±0.14)水平明显降低,差异具有统计学意义(χ^(2)=18.386,t=2.615~12.290,均P<0.05);重度PE[OR(95%CI)=1.708(1.193~2.445)]、收缩压[OR(95%CI)=1.495(1.090~2.049)]、舒张压[OR(95%CI)=1.621(1.076~2.442)]是影响HDCP患者发生不良妊娠结局的危险因素,DNMT1 mRNA[OR(95%CI)=0.833(0.725~0.957)],LncRNA UCA1[OR(95%CI)=0.796(0.696~0.909)]是影响HDCP患者发生不良妊娠结局的保护因素(均P<0.05);DNMT1 mRNA和LncRNA UCA1二者联合预测HDCP患者发生不良妊娠结局的曲线下面积(area under curve,AUC)大于DNMT1 mRNA及LncRNA UCA1单独预测的AUC(0.926 vs 0.832,0.844),差异具有统计学意义(Z=2.932,2.345,均P<0.05)。结论HDCP患者血清DNMT1 mRNA和LncRNA UCA1水平均较低,与病情程度、妊娠结局相关,DNMT1 mRNA联合LncRNA UCA1检测对不良妊娠结局有较佳预测效能。

Objective To analyze the relationship between the expression of serum DNA methyltransferase 1(DNMT1)messenger RNA(mRNA)and long non-coding RNA(LncRNA)urothelial carcinoembryonic antigen 1(UCA1)levels and pregnancy outcomes in patients with hypertensive disorder complicating pregnancy(HDCP).Methods A total of 195 HDCP patients treated in Handan Maternal and Child Health Hospital from March 2021 to August 2023 were selected as the case group,and 195 healthy pregnant women were regarded as the control group.Clinical data of all pregnant women were collected,and biochemical indicators were detected 1 day before delivery.Serum DNMT1 mRNA and LncRNA UCA1 levels were detected by fluorescence quantitative PCR.The case group was divided into pregnancy induced hypertension(PIH)group,mild preeclampsia(PE)group,and severe PE group based on their condition.HDCP patients were divided into good pregnancy outcome group and bad pregnancy outcome group according to the adverse pregnancy outcome at delivery.Clinical data,biochemical indexes,serum DNMT1 mRNA and LncRNA UCA1 levels were compared between control group and case group.The serum DNMT1 mRNA and LncRNA UCA1 levels of HDCP patients with different severity were compared.The clinical data,biochemical indexes,serum DNMT1 mRNA and LncRNA UCA1 levels of HDCP patients with different pregnancy outcomes were compared.The correlation between serum DNMT1 mRNA and LncRNA UCA1 in HDCP patients,factors affecting pregnancy outcomes in HDCP patients,and the predictive value of serum DNMT1 mRNA and LncRNA UCA1 in adverse pregnancy outcomes in HDCP patients were analyzed.Results Compared with control group,the levels of systolic blood pressure,diastolic blood pressure and white blood cell count in case group were increased,while the levels of serum DNMT1 mRNA(0.72±0.18 vs 1.00±0.04)and LncRNA UCA1(0.61±0.16 vs 1.00±0.02)were decreased,and the differences were statistically significant(t=40.651,32.595,7.837,21.205,33.775,all P<0.001).Serum DNMT1 mRNA(0.85±0.20,0.74±0.18,0.50±0.15)and LncRNA UCA1(0.77±0.18,0.58±0.16,0.43±0.13)levels in PIH group,mild PE group and severe PE group were decreased successively,and the differeences were statistically significant(F=52.687,64.030,all P<0.001).Serum DNMT1 mRNA in HDCP patients was positively correlated with LncRNA UCA1(r=0.582,P<0.001).Compared with good pregnancy outcome group,the severity of HDCP,systolic blood pressure,diastolic blood pressure and white blood cell count were increased in the bad pregnancy outcome group,and the serum DNMT1 mRNA(0.80±0.20 vs 0.59±0.15)and LncRNA UCA1(0.72±0.17 vs 0.43±0.14)levels were decreased,and the differences were statistically significant(χ^(2)=18.386,t=2.615~12.290,all P<0.05).Severe PE[OR(95%CI)=1.708(1.193~2.445)],systolic blood pressure[OR(95%CI)=1.495(1.090~2.049)]and diastolic blood pressure[OR(95%CI)=1.621(1.076~2.442)]were risk factors for adverse pregnancy outcomes in HDCP patients,while DNMT1 mRNA[OR(95%CI)=0.833(0.725~0.957)]and LncRNA UCA1[OR(95%CI)=0.796(0.696~0.909)]were protective factors for adverse pregnancy outcomes in HDCP patients(all P<0.05).The area under curve(AUC)predicted by the combination of DNMT1 mRNA and LncRNA UCA1 for adverse pregnancy outcomes in HDCP patients was greater than that predicted by DNMT1 mRNA alone and LncRNA UCA1 alone(0.926 vs 0.832,0.844),and the differences were statistically significant(Z=2.932,2.345,all P<0.05).Conclusion Both serum DNMT1 mRNA and LncRNA UCA1 levels are low in HDCP patients,which is related to the degree of disease and pregnancy outcome.DNMT1 mRNA combined with LncRNA UCA1 detection may have a better predictive effect on adverse pregnancy outcome.