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| Analysis of the pre-thrombotic status and the correlation study of MTHFR gene C677T polymorphism in women with recurrent spontaneous abortion |
| SONG Jinlong1 CHEN Pingping1 WANG Pengkun1 LAI Maohua2 MA Hongxia2 LI Juan2 |
1.Department of Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangdong Province, Guangzhou 510120, China;
2.Department of Chinese Medicine, the First Affiliated Hospital of Guangzhou Medical University, Guangdong Province, Guangzhou 510120, China |
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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.
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[1] 中华医学会妇产科学分会产科学组.复发性流产诊治的专家共识[J].中华妇产科杂志，2016，51（1）：3-9.
[2] Lin QD，Qiu LH. Pathogenesis，diagnosis，and treatment of recurrent spontaneous abortion with immune type [J]. Front Med China，2010，4（3）：275-279.
[3] Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion [J]. Fertil Steril，2008，90（5）：978-980.
[4] Rey E，Kahn SR，David M，et al. Thrombophilic disorders and fetal loss：a meta-analysis [J]. Lancet，2003，361（9361）：901-908.
[5] Gorana M，Aleksandra NM，Ljubica P，et al. Thromboprophylaxis implementation during pregnancy in women with recurrent foetal losses and thrombophilia [J]. Med Pregl，2011，64（9/10）：471-475.
[6] Gon?觭alves RO，Fraga LR，Santos WVB，et al. Association between the thrombophilic polymorphisms MTHFR C677T，Factor V Leiden，and prothrombin G20210A and recurrent miscarriage in Brazilian women [J]. Genet Mol Res，2016，15（3）：15038156.
[7] 王谢桐.不良妊娠结局妇女遗传性易栓症相关基因多态性和血凝抑制因子的研究[D].济南：山东大学，2005.
[8] Kumar KS，Govindaiah V，Naushad SE，et al. Plasma homocysteine levels correlated to interactions between folate status and methylene tetrahydrofolate reductase gene mutation in women with unexplained recurrent pregnancy loss [J]. J Obstet Gynaecol，2003，23（1）：55-58.
[9] El Achi H，Awwad J，Abou Daya S，et al. The association between cardiovascular disease gee mutations and recurrent pregnancy loss in the Lebanese population [J]. Mol Biol Rep，2018，45（5）：911-916.
[10] Engbersen AM，Franken DG，Boers GH，et al. Thermolabile 5,10-methylenetetra-hydrofolate reductase as a cause of mild hyperhomocysteinemia [J]. Am J Hum Genet，1995，56（1）：142-150.
[11] Molls S，Varga EA. Homocysteine and MTHFR Mutations [J]. Circulation，2015，132（1）：e6-e9.
[12] Serapinas D，Boreikaite E，Bartkevicitue A，et al. The improtance of folate，vitamins B6 and B12 for the lowering of homocysteine concentrations for patients with recurrent pregnancy loss and MTHFR mutations [J]. Reprod Toxicol，2017，72：159-163.
[13] 于鹏跃，赵凤莲，张晓华，等.血栓弹力图、平均血小板体积/血小板计数比值和纤维蛋白原水平对复发性流产的预测价值[J].吉林大学学报：医学版，2020，46（1）：127-131.
[14] 李晓丹，张锋，陈海迎，等.血栓前状态指标与不明原因复发性流产的相关性研究[J].浙江医学，2018，40（20）：2230-2232.
[15] 舒利琼，冉曦，杜春兰，等.血小板和凝血功能筛查对复发性流产监测的临床意义研究[J].国际检验医学杂志，2020，41（3）：366-368.
[16] 王楠，王妍，赵扬玉.蛋白S缺乏症与产科并发症研究现状[J].中国妇产科临床杂志，2018，19（3）：280-281.
[17] D?覥uski D，Mierzyński R，Poniedzia?覥ek-Czajkowska E，et al. Adverse pregnancy outcomes and inherited thrombophi-lia [J]. J Perinat Med，2018，46（4）：411-417.
[18] 杨芳.妊娠期易栓症患者凝血相关指标的改变及抗凝治疗的临床价值研究[J].中国实用医药，2015，21（11）：188-189.
[19] 刘玮.早期复发性流产的病因分析及易栓症标志物抗凝血酶-Ⅲ、蛋白C、蛋白S与不明原因复发性流产的相关性研究[D].合肥：安徽医科大学，2017.
[20] 刘英光，崔银杰.小剂量阿司匹林与低分子肝素联合治疗妊娠期易栓症疗效的研究[J].医学理论与实践，2012， 25（4）：439-441.
[21] 肖金生，王厚照.8项凝血相关指标与复发性流产的相关性研究[J].国际医药卫生导报，2018，24（7）：1092-1094.
[22] Julia BM，Marina L，Ricardo G，et al. Interaction between MTHFR 677C> T，PON1 192Q> R and PON1 55L> M polymorphisms and its effect on non-recurrent spontaneous abortion in Mexican women [J]. Gene，2019，20（689）：69-75.
[23] Servy EJ，Jacquesson-Fournols L，Cohen M，et al. MTHFR isoform carriers. 5-MTHF （5- methyl tetrahydrofolate） vs folic acid：a key to pregnancy outcome：a case series [J]. J Assist Reprod Genet，2018，35（8）：1431-1435.
[24] Chen H，Yang X，Lu M. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China：a systematic review and meta-analysis [J]. Arch Gynecol Obstet，2016，293（2）：283-290.
[25] Rai V. Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population：A Meta-analysis [J]. Indian J Clin Biochem，2016，31（4）：402-413. |
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