Correlation between MTHFR gene C677T and A1298C polymorphisms and plasma homocysteine in recurrent abortion
ZHAO Ai1 ZHANG Li1 MENG Lin2
1.Department of Obstetrics, Huai’an First People’s Hospital, Jiangsu Province, Huai’an 223300, China;
2.Department of Obstetrics, Affiliated Hospital of Xuzhou Medical University, Jiangsu Province, Xuzhou 221000, China
Abstract Objective To investigate the correlation between MTHFR gene C677T and A1298C polymorphisms and plasma homocysteine in recurrent abortion. Methods A total of 100 women with recurrent abortion admitted to Huai’an First People’s Hospital, Jiangsu Province were selected as the recurrent abortion group, and 100 women with a history of one childbirth without history of adverse pregnancy were selected as the control group from December 2016 to June 2019. Restriction fragment length polymorphisms were used to detect the MTHFR gene C677T and A1298C genotypes; the occurrence risk of recurrent abortion with different genotypes was analyzed; colorimetric method was used to detect homocysteine level; the differences in homocysteine level between different genotypes were compared. Results There were statistically significant differences in the genotypes of C677T and A1298C between the two groups (all P < 0.05). Compared with C677T CC type, C677T TT type had a 3.375-fold increased risk of recurrent abortion (P = 0.008); Compared with A1298C AA type, A1298C CC had a 3.721-fold increased risk of recurrent abortion (P = 0.012). The homocysteine level in the recurrent abortion group was higher than that in the control group, and the difference was statistically significant (P < 0.05). Homocysteine level of C677T TT type was higher than that C677T CC type and C677T CT type, and the difference was statistically significant (P < 0.05); homocysteine level of A1298C CC type was higher than that of A1298C AA type and A1298C AC type, and the difference was statistically significant (P < 0.05). Conclusion The MTHFR gene C677T TT type and A1298C CC type have a higher risk of recurrent abortion, and C677T and A1298C polymorphisms can lead to elevated homocysteine level. The MTHFR gene C677T and A1298C mutations may be involved in the pathogenesis of recurrent abortion by changing homocysteine level.
[1] Shahine L，Lathi R. Recurrent pregnancy loss：evaluation and treatment [J]. Obstet Gynecol Clin North Am，2015， 42（1）：117-134.
[2] Hansen KA. What Is New in Recurrent Miscarriage?：Best Articles From the Past Year [J]. Obstet Gynecol，2017，130（6）：1380-1382.
[3] 黄凌云，沈晔，钱芳波.FMR1基因突变与自然流产及复发性流产的相关性研究[J].实用医院临床杂志，2020，17（5）：23-26.
[4] 卞义华，吴晓丽，马凤英，等.复发性流产夫妇相关病因分析[J].临床和实验医学杂志，2020，19（16）：1723-1726.
[5] 蒋武，鲁衍强，李瑛，等.南宁市汉族女性不明原因复发性流产与MTHFR基因C677T位点多态性相关性研究[J].广西医科大学学报，2017，34（12）：1728-1730.
[6] 黄中秀，李小兰，李小松.MTHFR基因C677T及A1298C多态性与自然流产的关系[J].医学综述，2020，26（11）：2275-2278，2283.
[7] 许雅娟，班彦杰，冉利敏，等.MTHFR基因多态性与不明原因复发性流产的关系[J].郑州大学学报：医学版，2020， 55（1）：112-115.
[8] Puri M，Kaur L，Walia GK，et al. MTHFR C677T polymorphism，folate，vitamin B12 and homocysteine in recurrent pregnancy losses：a case control study among North Indian women [J]. J Perinat Med，2013，41（5）：549-554.
[9] 张亚丽，靳双玲，张春燕，等.亚甲基四氢叶酸还原酶基因多态性在妇产科领域的研究进展[J].国际妇产科学杂志，2020，47（4）：394-398.
[10] 李小兰，林琼珊，鲁衍强，等.先兆流产与MTHFR、MTRR基因多态性的关系[J].重庆医学，2017，46（6）：770-772.
[11] 杨新鸣，郭书娴，王宇，等.高同型半胱氨酸与PCOS先兆流产的研究进展[J].现代中西医结合杂志，2020，29（26）：2960-2964.
[12] 华知奋，黄彩梅，鲁衍强，等.MTHFR基因多态性与原因不明复发性流产的相关性研究[J].国际检验医学杂志，2017，38（1）：16-17.
[13] 黄山鹰，唐国玲，刘庆芝，等.MTHFR的基因多态性与原因不明复发性流产的相关性分析[J].国际生殖健康/计划生育杂志，2017，36（5）：382-384.
[14] Knight KM，Hackney DN. Re-evaluation of the subgroup analysis from the Royal College of Obstetricians and Gynaecologists randomized controlled trial of cervical cerclage [J]. J Matern Fetal Neonatal Med，2012，25（6）：864-865.
[15] 王连，郝胜菊，闫有圣，等.血浆Hcy水平及MTHFR和MTRR基因多态性与复发性流产的相关性研究[J].中国优生与遗传杂志，2017，25（7）：18-19，17.
[16] 申华，冯杏琳，罗素霞，等.MTHFR基因677位点多态性及HCY与复发性流产[J].中国优生与遗传杂志，2017， 25（10）：7，20.
[17] 刘英华，刘敏娟，向菁菁，等.叶酸代谢酶MTHFR基因多态性与不明原因复发性流产的相关性研究[J].中国优生与遗传杂志，2019，27（1）：6-7，21.
[18] 徐佳佳，梁玲芝，陈贤君，等.MTHFR基因多态性与先兆流产和复发性流产的关系[J].中国妇幼保健，2019， 34（6）：1326-1328.
[19] 苏占营，吴成亮，辜敏，等.血清同型半胱氨酸与D-二聚体、叶酸、维生素B12联合检测对复发性流产早期预防的意义[J].实验与检验医学，2020，38（4）：687-688， 691.
[20] 奚婷，包晓霞，许梦白，等.复发性流产相关基因的生物信息学分析[J].中华中医药学刊，2020，38（5）：142-146， 280-281.
[21] Jusic A，Balic D，Avdic A，et al. The association of factor V G1961A （factor V Leiden），prothrombin G20210A，MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women [J]. Med Glas（Zenica），2018，15（2）：158-163.
[22] Sah AK，Shrestha N，Joshi P，et al. Association of parental methylenetetrahydrofolate reductase（MTHFR）C677T gene polymorphism in couples with unexplained recurrent pregnancy loss [J]. BMC Res Notes，2018，11（1）：233.
[23] Pereza N，Ostojic S，Kapovic M，et al. Systematic review and meta-analysis of genetic association studies in idiopathic recurrent spontaneous abortion [J]. Fertil Steril，2017，107（1）：150-159.
[24] Zaric BL，Obradovic M，Bajic V，et al. Homocysteine and Hyperhomocysteinaemia [J]. Curr Med Chem，2019，26（16）：2948-2961.
[25] Zarfeshan FY，Kooshkaki O，Kordi TD，et al. Investigation of the association between C677T polymorphism of the MTHFR gene and plasma homocysteine level in recurrent fetal miscarriage [J]. J Obstet Gynaecol Res，2019， 45（8）：1442-1447.
