复发性流产患者血栓前状态分析及其与MTHFR基因C677T位点多态性的相关性研究

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摘要目的探讨复发性自然流产（RSA）与凝血相关指标之间的关系，以及亚甲基四氢叶酸还原酶（MTHFR）基因C677T位点多态性与RSA遗传易感性的相关性。方法选择2018年9月—2019年3月就诊于广州医科大学附属第一医院RSA患者77例为RSA组，另选择41名正常健康女性为正常对照组。采集两组人群EDTA抗凝全血，比较两组人群凝血指标和易栓症标志物的差异。对MTHFR基因通过聚合酶链式反应（PCR）扩增后进行Sanger法测序，分析比较两组MTHFR基因C677T位点的基因多态性。结果 RSA组纤维蛋白原（FIB）水平高于正常对照组，差异有统计学意义（P ＜ 0.05）。RSA组蛋白S（PS）缺陷发生率高于正常对照组，差异有统计学意义（P ＜ 0.05）。以PS判断RSA患者存在血栓前状态（PTS）的最佳临界值为45%，曲线下面积为0.701（95%CI：0.611～0.791，P < 0.01），灵敏度为95.1%，特异度为42.9%。两组人群中基因型比较，差异有统计学意义（P ＜ 0.05）。两组人群等位基因频率比较，差异有统计学意义（P ＜ 0.05）。结论 FIB水平升高及PS缺陷可能与RSA的发生相关，可作为RSA的筛查指标，且PS缺陷对于RSA的判断具有一定的参考价值。MTHFR基因多态位点C677T的突变可能为RSA发病的原因之一。

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	宋金龙1 陈萍萍1 王鹏鲲1 赖毛华2 马红霞2 李娟2

关键词 ：复发性流产, 亚甲基四氢叶酸还原酶, 基因多态性, 凝血指标, 易栓症标志物

Abstract：Objective To explore the relationship between recurrent spontaneous abortion (RSA) and coagulation-related indicators, as well as the relationship between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and the genetic susceptibility to RSA. Methods A total of 77 RSA patients in the First Affiliated Hospital of Guangzhou Medical University from September 2018 to March 2019 were selected as the RSA group, and a total of 41 normal healthy women were selected as the normal control group. EDTA anticoagulated whole blood was collected from two groups, and the differences in coagulation indicators and markers of thrombosis were compared between the two groups. The MTHFR gene was amplified by polymerase chain reaction (PCR) and then sequenced by Sanger method, and the genetic polymorphisms of MTHFR gene C677T polymorphism of the two groups were analyzed and compared. Results The fibrinogen (FIB) level of the RSA group was higher than that of the normal control group, the difference was statistically significant (P ＜ 0.05). The incidence of PS defects in the RSA group was higher than that in the normal control group, and the difference was statistically significant (P ＜ 0.05). The best cut-off value of PS to judge the existence of prethrombotic state (PTS) in RSA patients was 45%, the area under the curve was 0.701 (95%CI: 0.611-0.791, P < 0.01), the sensitivity was 95.1%, and the specificity was 42.9%. There was a statistically significant difference in genotype comparison between the two groups of people (P ＜ 0.05). The comparison of allele frequencies between the two groups showed statistically significant differences (P ＜ 0.05). Conclusion FIB levels and PS defects may be related to the occurrence of RSA, which can be used as screening indicators for RSA, and PS defects have a certain reference value for the judgment of RSA. MTHFR gene polymorphic site C677T mutation may be one of the causes of RSA.

Key words： Recurrent spontaneous abortion Methylenetetrahydrofolate reductase Polymorphism of gene Clotting indicators Markers of thrombosis

基金资助:国家自然科学基金资助项目（81804137）；
广东省省级科技计划项目（2017A020213004）。

通讯作者: 李娟（1985.5-），女，博士，副主任医师；研究方向：中西医结合防治生殖内分泌疾病。

引用本文:

宋金龙1 陈萍萍1 王鹏鲲1 赖毛华2 马红霞2 李娟2. 复发性流产患者血栓前状态分析及其与MTHFR基因C677T位点多态性的相关性研究[J]. 中国医药导报, 2020, 17(31): 16-20.
SONG Jinlong1 CHEN Pingping1 WANG Pengkun1 LAI Maohua2 MA Hongxia2 LI Juan2. Analysis of the pre-thrombotic status and the correlation study of MTHFR gene C677T polymorphism in women with recurrent spontaneous abortion. 中国医药导报, 2020, 17(31): 16-20.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2020/V17/I31/16

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