多次流产患者血栓前状态相关标志物的检测与分析  

Detection and analysis of markers related to prethrombotic status in patients with multiple abortions

作　　者：刘宁 王超[1] 刘羽[1] 王瑞静 张玉红[1] 张婷[1] 田婷婷 刘梅梅[1] LIU Ning;WANG Chao;LIU Yu;WANG Rui-jing;ZHANG Yu-hong;ZHANG Ting;TIAN Ting-ting;LIU Mei-mei(Department of Obstetrics and Gynecology,The Second Affiliated Hospital of Harbin Medical University,Harbin 150086)

机构地区：[1]哈尔滨医科大学附属第二医院妇产科,哈尔滨150086

出　　处：《生殖医学杂志》2022年第9期1226-1231,共6页Journal of Reproductive Medicine

基　　金：吴阶平基金项目[320.6750.18558(10)]。

摘　　要：目的比较血栓前状态(PTS)相关标志物在多次流产人群和正常对照人群中的差异,分析其对于多次流产发生的影响。方法回顾性分析2019年12月至2021年5月就诊于我院妇产科门诊的324例人员临床资料。根据既往妊娠情况分为病例组(发生2次及以上自然流产的患者,n=193)和对照组(无自然流产史且有过正常生育史的女性,n=131),比较两组研究对象的年龄、体质量指数(BMI)、同型半胱氨酸(HCY)水平,采用Logistic回归模型对年龄、BMI、HCY、蛋白C(PC)和蛋白S(PS)活性、凝血因子V(FⅤ)1691、凝血酶原(FⅡ)20210、纤溶酶原激活物抑制剂-1(PAI-1)675、亚甲基四氢叶酸还原酶(MTHFR)677及1298、甲硫氨酸合成酶还原酶(MTRR)66位点的基因多态性进行单因素和多因素分析,并采用受试者工作特征曲线(ROC)对模型进行评价。结果两组研究对象的年龄、BMI平均值及HCY水平比较均无显著性差异(P>0.05)。两组研究对象均未发现FⅤ(1691)、FⅡ(20210)位点的多态性突变,而PAI-1(675)、MTHFR(677)、MTHFR(1298)及MTRR(66)位点均检测到多态性突变。单因素分析结果显示,BMI、PAI-1(675)、MTRR(66)位点多态性在两组中有显著性差异(P<0.05);多因素分析结果显示,BMI>24 kg/m^(2)、PAI-1基因675位点由5G突变为4G和MTHFR基因677位点由C突变为T可能是发生多次流产的独立危险因素(P<0.05);ROC结果显示,预测模型的曲线下面积(AUC)为0.664,灵敏度为54.9%,特异度为70.2%。结论BMI>24 kg/m^(2)、PAI-1(675)和MTHFR(677)位点突变可能是发生多次流产的独立危险因素,但其具体机制尚不明确,尚需后续研究加以验证探讨。Objective:To compare the changes of prothrombotic status(PTS)related markers in the multiple abortion population and the normal controls,and analyze their effect on the occurrence of multiple abortions.Methods:The clinical data of 324 women who visited the outpatient department of obstetrics and gynecology in our hospital from December 2019 to May 2021 were retrospectively analyzed.According to previous pregnancy history,they were divided into a case group(patients with two or more spontaneous abortions,n=193)and a control group(women without spontaneous abortion and with normal reproductive history,n=131).Age,body mass index(BMI),homocysteine(HCY)level were compared between the groups.Univariate and multivariate analysis was performed by logistic regression model for age,BMI,HCY,activity of protein C(PC)and protein S(PS),coagulation factor V(FV)1691,prothrombin(FII)20210,plasminogen activator inhibitor-1(PAI-1)675,methylenetetrahydrofolate reductase(MTHFR)677 and 1298,methionine synthase reductase(MTRR)66 gene polymorphisms,and the receiver operating characteristic(ROC)curve was used to evaluate the model.Results:There were no significant differences in age,average BMI and HCY levels between the two groups(P>0.05).No polymorphic mutations at FV(1691)and FII(20210)sites were found in the both groups,while polymorphic mutations were detected at PAI-1(675),MTHFR(677),MTHFR(1298)and MTRR(66).Univariate analysis showed that there were significant differences in BMI,PAI-1(675)and MTRR(66)polymorphisms between the two groups(P<0.05).Multivariate analysis showed that BMI>24 kg/m^(2),PAI-1 gene 675 locus mutation from 5G to 4G and MTHFR gene 677 locus mutation from C to T may be the independent risk factors for multiple abortion(P<0.05).The area under the curve(AUC)in the ROC evaluation was 0.664,the sensitivity was 54.9%,and the specificity was 70.2%.Conclusions:BMI>24 kg/m^(2),mutations at PAI-1(675)and MTHFR(677)sites may be the independent risk factors for multiple abortion,but the specific mechanism is not clear,and

关 键 词：自然流产 血栓前状态 LOGISTIC回归模型 基因多态性 

分 类 号：R715.5[医药卫生—妇产科学]