[1]侯书利,张金玲,李 燕,等.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[J].现代检验医学杂志,2024,39(05):47-53.[doi:10.3969/j.issn.1671-7414.2024.05.009]
　HOU Shuli,ZHANG Jinling,LI Yan,et al.Relationship between the Expression of Serum DNMT1 mRNA and LncRNA UCA1 Levels and Pregnancy Outcome in Patients with Hypertensive Disorder Complicating Pregnancy[J].Journal of Modern Laboratory Medicine,2024,39(05):47-53.[doi:10.3969/j.issn.1671-7414.2024.05.009]
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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()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年05期
页码:
47-53
栏目:
论著
出版日期:
2024-09-15

文章信息/Info

Title:
Relationship between the Expression of Serum DNMT1 mRNA and LncRNA UCA1 Levels and Pregnancy Outcome in Patients with Hypertensive Disorder Complicating Pregnancy
文章编号:
1671-7414（2024）05-047-07
作者:
侯书利; 张金玲; 李 燕; 李晓晓
（邯郸市妇幼保健院产五科，河北邯郸 056001）
Author(s):
HOU Shuli;  ZHANG Jinling;  LI Yan;  LI Xiaoxiao
（Department of Obstetrics and Gynecology, Handan Maternal and Child Health Hospital, Hebei Handan 056001, China）
关键词:
妊娠期高血压疾病; DNA 甲基转移酶1 信使RNA; 长链非编码RNA 尿路上皮癌胚抗原1; 妊娠结局
分类号:
R714.246；R392.11
DOI:
10.3969/j.issn.1671-7414.2024.05.009
文献标志码:
A
摘要:
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（χ2=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。
Abstract:
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 (χ2=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.

参考文献/References:

[1] COGGINS N, LAI S. Hypertensive disorders of pregnancy[ J]. Emergency Medicine Clinics of North America, 2023, 41(2): 269-280.
[2] 颜雪梅, 孔繁娟, 王爱华, 等. 2012-2019 年妊娠期高血压疾病流行现状及妊娠结局分析[J]. 中国生育健康杂志, 2021, 32(3): 252-256. YAN Xuemei, KONG Fanjuan, WANG Aihua, et al. Prevalence of hypertensive diseases in pregnancy and analysis of pregnancy outcomes from 2012 to 2019[J]. Chinese Journal of Reproductive Health, 2021, 32(3): 252-256.
[3] 王维, 唐静, 杨永红, 等. 妊娠期高血压疾病患者胎盘组织叶酸代谢基因MTR 的表达水平及其作用机制研究[J]. 现代检验医学杂志, 2022, 37(4): 134-138, 173. WANG Wei, TANG Jing, YANG Yonghong, et al. Expression level and effects of folate metabolismrelated gene MTR in placenta of patients with hypertensive disorder complicating pregnancy[J]. Journal of Modern Laboratory Medicine, 2022, 37(4): 134-138, 173.
[4] DING Xiaobao, LIN Yuwen, CHEN Chen, et al. DNMT1 mediates chronic pain-related depression by inhibiting GABAergic neuronal activation in the central amygdala[J]. Biological Psychiatry, 2023, 94(8): 672-684.
[5] 马晓莉, 吴凯, 张辉, 等. DNA 甲基转移酶1 在一氧化氮合酶抑制剂诱导的滋养细胞自噬中的作用[J].实用医学杂志, 2019, 35(1): 14-18. MA Xiaoli, WU Kai, ZHANG Hui, et al. Role of DNMT1 in trophoblast autophagy induced by nitric oxide synthase inhibitors[J]. The Journal of Practical Medicine, 2019, 35(1): 14-18.
[6] 钟黎黎, 盛莹, 郭江虹, 等. LncRNA-UCA1 通过靶向调控miR-182-5p 对滋养细胞侵袭与转移的影响[J]. 山东大学学报( 医学版), 2022, 60(3): 76-82. ZHONG Lili, SHENG Ying, GUO Jianghong, et al. LncRNA-UCA1 effects invasion and metastasis of trophoblast cells by targeting miR-182-5p[J]. Journal of Shandong University (Health Science), 2022, 60(3): 76-82.
[7] 中华医学会妇产科学分会妊娠期高血压疾病学组.妊娠期高血压疾病诊治指南(2020)[J]. 中华妇产科杂志, 2020, 55(4): 227-238. Hypertensive Disorders in Pregnancy Subgroup, Chinese Society of Obstetrics and Gynecology, Chinese Medical Association. Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020)[J]. Chinese Journal of Obstetrics and Gynecology, 2020, 55(4): 227-238.
[8] JIANG Li, TANG Kun, MAGEE L A, et al. A global view of hypertensive disorders and diabetes mellitus during pregnancy[J]. Nature Reviews Endocrinology, 2022, 18(12): 760-775.
[9] MALEK A M, WILSON D A, TURAN T N, et al. Incident heart failure within the first and fifth year after delivery among women with hypertensive disorders of pregnancy and prepregnancy hypertension in a diverse population[J]. Journal of the American Heart Association, 2021, 10(17): e021616.
[10] WU Ying, WU Yue, DUAN Lihong, et al. Clinical meaning of serum trimethylamine oxide, N-terminalpro- brain natriuretic peptide, hypoxia-inducible factor- 1a and left ventricular function and pregnancy outcome in patients with pregnancy-induced hypertension[J]. Journal of Medical Biochemistry, 2023, 42(2): 265-273.
[11] 王莉, 赵霞, 吴莎, 等. 妊娠期高血压疾病300 例妊娠结局分析[J]. 中国实用妇科与产科杂志, 2021,37(5): 588-591. WANG Li, ZHAO Xia, WU Sha, et al. Analysis of pregnancy outcome of women with hypertensive diseases during pregnancy[J]. Chinese Journal of Practical Gynecology and Obstetrics, 2021, 37(5): 588-591.
[12] ZHANG Yan, LI Huan, GUO Wenting, et al. Predictive value of coagulation function and D-dimer for pregnancy outcome in pregnancy-induced hypertension[J]. American Journal of Translational Research, 2023, 15(2): 1150-1158.
[13] 陈莉, 张丛丛, 李青山, 等. AML 和ALL 患者骨髓DNMT1, SFRP1 基因甲基化及其与临床病理特征和预后相关性研究[J]. 现代检验医学杂志, 2022,37(6): 7-13. CHEN Li, ZHANG Congcong, LI Qingshan, et al. Methylation of DNMT1 and SFRP1 gene in bone marrow and its correlation with clinicopathological features and prognosis in patients with AML and ALL[J]. Journal of Modern Laboratory Medicine, 2022, 37(6): 7-13.
[14] GENG Xueying, ZHAO Jun, HUANG Jiayu, et al. Lnc-MAP3K13-7:1 inhibits ovarian GC proliferation in PCOS via DNMT1 downregulation-mediated CDKN1A promoter hypomethylation[J]. Molecular Therapy, 2021, 29(3): 1279-1293.
[15] FRAZIER S, MCBRIDE M W, MULVANA H, et al. From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia[J]. Clinical Science (London, England: 1979), 2020, 134(8): 1001-1025.
[16] 李静, 于学文, 杨洋, 等. 不明原因复发性流产患者绒毛组织中DNA 低甲基化及机制[J]. 细胞与分子免疫学杂志, 2019, 35(4): 351-356. LI Jing, YU Xuewen, YANG Yang, et al. DNA hypomethylation in villi of patients with unexplained recurrent spontaneous abortion and its mechanism[J]. Chinese Journal of Cellular and Molecular Immunology, 2019, 35(4): 351-356.
[17] HU Mengsi, WANG Yao, MENG Yanping, et al. Hypoxia induced-disruption of LncRNA TUG1/PRC2 interaction impairs human trophoblast invasion through epigenetically activating Nodal/ALK7 signalling[J]. Journal of Cellular and Molecular Medicine, 2022, 26(14): 4087-4100.
[18] LIU Tong, WANG Xia, ZHAI Jingfang, et al. Long noncoding RNA UCA1 facilitates endometrial cancer development by regulating KLF5 and RXFP1 gene expressions[J]. Cancer Biotherapy & Radiopharmaceuticals, 2021, 36(6): 521-533.
[19] APICELLA C, RUANO C S M, JACQUES S, et al. Urothelial cancer associated 1 (UCA1) and miR-193 are two non-coding RNAs involved in trophoblast fusion and placental diseases[J]. Frontiers in Cell and Developmental Biology, 2021, 9: 633937.
[20] LI Jie, LU Yiling, WANG Ying, et al. Long noncoding RNA urothelial carcinoma associated 1 protects human placental vascular endothelial cells from hypoxiainduced damage by regulating the miR-197-3p/histone deacetylase-2 axis in patients with pregnancy-induced hypertension[J]. American Journal of Translational Research, 2022, 14(9): 6137-6149.
[21] SHAO Hongfang, JIN Feng, HU Jiangshan, et al. Urothelial carcinoma associated 1 promotes trophoblast invasion by regulating MMP9[J]. Cell and Bioscience, 2019, 9: 78.
[22] PAN Zhijie, ZHONG Bohuan, LING Xiaoxuan, et al. The DNMT1-associated LncRNA UCA1 was upregulated in TK6 cells transformed by long-term exposure to hydroquinone and benzene-exposed workers via DNA hypomethylation[J]. Journal of Biochemical and Molecular Toxicology, 2021, 35(12): e22920.

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备注/Memo

备注/Memo:
基金项目：河北省医学科学研究课题计划项目（20220442）。
作者简介：侯书利（1986-），女，本科，主治医师，研究方向：妊娠期高血压诊断，E-mail：houshuli984@sina.com。
通讯作者：李燕（1974-），女，本科，副主任医师，研究方向：妊娠期高血压诊断，E-mail：448562060@qq.com。
更新日期/Last Update: 2024-09-15