摘要
目的探究纤溶酶原激活物抑制物-1(PAI-1)基因4G/5G多态性与行羟氯喹联合肝素治疗不明原因复发性流产(URSA)患者妊娠结局的相关性。方法选取2019年1月至2021年1月肇庆市第一人民医院收治的138例URSA患者为研究对象,检测所有受试者PAI-1基因4G/5G位点基因多态性。患者均采用羟氯喹联合肝素治疗,根据妊娠结局分为良好妊娠结局组和不良妊娠结局组。观察两组间PAI-1基因4G/5G基因位点基因型及等位基因的分布差异,并分析PAI-1基因4G/5G位点基因多态性与行羟氯喹联合肝素治疗URSA患者妊娠结局的相关性。结果138例患者中117例患者在治疗后妊娠成功,妊娠成功率为84.78%(117/138)。117例妊娠成功的患者中6例失访,失访率为5.13%(6/117)。111例患者中流产22例,低体质量儿6例,死胎、新生儿死亡各2例,不良妊娠结局发生率为28.83%(32/111)。两组职业类别、工作性质、PAI-1基因型分布比较差异有统计学意义(P<0.05或P<0.01),不良妊娠结局组大专及以上的比例低于良好妊娠结局组[37.50%(12/32)比60.76%(48/79)](P<0.05),生化妊娠史占比高于良好妊娠结局组[81.25%(26/32)比50.63%(40/79)](P<0.01)。不良妊娠结局组PAI-1基因4G等位基因频率高于良好妊娠结局组[65.63%(42/64)比37.97%(60/158)](P<0.01)。多因素Logistic回归分析结果显示,PAI-1基因型4G/4G、4G等位基因及生化妊娠史是行羟氯喹联合肝素治疗URSA患者不良妊娠结局发生的危险因素(OR=3.747,95%CI 1.470~6.024;OR=4.204,95%CI 1.672~6.736;OR=2.672,95%CI 1.269~4.076)(P<0.01)。结论PAI-1基因型4G/4G和4G等位基因与行羟氯喹联合肝素治疗URSA患者发生不良妊娠结局关系密切,是导致行羟氯喹联合肝素治疗URSA患者不良妊娠结局发生的危险因素。
Objective To explore the correlation between the 4G/5G polymorphism of plasminogen activator inhibitor-1(PAI-1)gene and pregnancy outcomes in patients treated with hydroxychloroquine combined with heparin for unexplained recurrent spontaneous abortion(URSA).Methods A total of 138 patients with URSA treated in Zhaoqing First People′s Hospital from Jan.2019 to Jan.2021 were included.The 4G/5G polymorphisms of PAI-1 gene were detected in all subjects.All of the patients were treated with hydroxychloroquine combined with heparin,and were divided into a good pregnancy outcome group and a bad pregnancy outcome group according to the pregnancy outcome.The differences in the distribution of 4G/5G genotype and alleles of PAI-1 gene between the two groups were observed,and the correlation between the 4G/5G polymorphism of PAI-1 gene and pregnancy outcomes in patients treated with hydroxychloroquine combined with heparin for URSA was analyzed.Results Among the 138 patients,117 had a successful pregnancy after treatment,and the pregnancy success rate was 84.78%(117/138).Among the 117 successful pregnancies,6 cases were lost to follow-up,with a loss rate of 5.13%(6/117).Among the remaining 111 patients,22 had abortion,6 had low body weight infants,2 were stillbirths and 2 were neonatal deaths,and the incidence of adverse pregnancy outcome was 28.83%(32/111).There were statistically significant differences in occupational category,job nature and PAI-1 genotype between the two groups(P<0.05).The proportion of a college degree or above in the adverse pregnancy outcome group was lower than that in the good pregnancy outcome group[37.50%(12/32)vs 60.76%(48/79)](P<0.05),the percentage of biochemical pregnancy history was higher than that in the good pregnancy outcome group[81.25%(26/32)vs 50.63%(40/79)](P<0.01).The 4G allele frequency of the PAI-1 gene was higher in the bad pregnancy outcome group than in the good pregnancy outcome group[65.63%(42/64)vs 37.97%(60/158)](P<0.01).The results of the multivariate Logistic regression analysis showed that,PAI-1 genotype 4G/4G,4G alleles and biochemical pregnancy history were risk factors for adverse pregnancy outcomes in the URSA patients treated with hydroxychloroquine combined with heparin(OR=3.747,95%CI 1.470-6.024;OR=4.204,95%CI 1.672-6.736;OR=2.672,95%CI 1.269-4.076)(P<0.01).Conclusion The 4G/4G and 4G alleles of PAI-1 genotype are closely related to adverse pregnancy outcomes in URSA patients treated with hydroxychloroquine combined with heparin,and are risk factors for adverse pregnancy outcomes in the patients.
作者
彭顺英
赵花
李琼珍
黄芳
文春梅
PENG Shunying;ZHAO Hua;LI Qiongzhen;HUANG Fang;WEN Chunmei(Reproductive Infertility Center,the First People′s Hospital of Zhaoqing,Zhaoqing 526000,China)
出处
《医学综述》
CAS
2023年第24期5886-5890,5898,共6页
Medical Recapitulate
基金
肇庆市科技计划项目(2019N009)。
关键词
不明原因复发性流产
纤溶酶原激活物抑制物-1基因
基因多态性
羟氯喹
肝素
妊娠结局
Unexplained recurrent spontaneous abortion
Plasminogen activator inhibitor-1 gene
Gene polymorphism
Hydroxychloroquine
Heparin
Pregnancy outcome
