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MTHFR、MTRR基因多态性与不明原因复发性流产研究

2020-09-02李伏福源志群周运花黄玉梅

中外医疗 2020年16期
关键词:叶酸复发性等位基因

李伏福 源志群 周运花 黄玉梅

[摘要] 目的 探討5,10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点、A1298C 位点以及甲硫氨酸合成酶还原酶(MTRR )基因A66G 位点多态性与不明原因复发性流产关系。方法 采用病例对照研究办法,方便选取2017年7月— 2019年7月在该院生殖中心就诊的原因不明胎停育≥2次的130例患者为病例组,122例在该院产检孕周大于28周,无并发症的孕妇或者生育大于1个小孩的妇女且未发生过流产的患者作为对照组,比较病例组与对照组基因型,分析不明原因复发性流产与 MTHFR 基因 C677T 位点、A1298C 位点和 MTRR 基因 A66G 位点多态性关系。结果 MTHFR基因 C677T 位点中,病例组CC基因频率为30.77%,对照组CC基因频率为57.38%,差异有统计学意义(χ2=18.115,P<0.05);病例组CT基因频率为55.38%,对照组CT基因频率为37.70%,差异有统计学意义(χ2=7.900,P<0.05);病例组TT基因频率为13.85%,对照组TT基因频率为4.92%,差异有统计学意义(χ2=5.821,P<0.05);病例组C等位基因频率为58.46%,对照组C等位基因频率为76.23%,差异有统计学意义(χ2=32.389,P<0.05);病例组T等位基因频率为41.54%,对照组T等位基因频率为23.77%,差异有统计学意义(χ2=32.389,P<0.05)。两组患者在CC、CT、TT3种基因型、C等位基因、T等位基因的分布差异有统计学意义(P<0.05)。MTHFR基因 A1298C位点、MTRR 基因A66G 位点多态性病例组和对照组差异无统计学意义(P>0.05)。结论 C677T的TT型是复发性流产的高危因素,MTHFR基因多态性与不明原因复发性流产有一定的关系, MTHFR基因 A1298C位点、MTRR 基因A66G 位点多态性与不明原因复发性流产无明确关系。

[关键词] 复发性流产;不明原因复发性流产;MTHFR(5,10.亚甲基四氢叶酸还原酶);MTRR(甲硫氨酸合成酶还原酶);多态性

[中图分类号] R4          [文献标识码] A          [文章编号] 1674-0742(2020)06(a)-0016-04

Correlation between MTHFR and MTRR Gene Polymorphisms and Unexplained Recurrent Abortion

LI Fu-fu, YUAN Zhi-qun, ZHOU Yun-hua, HUANG Yu-mei

Reproductive Center of Meizhou Maternal and Child Health Family Planning Service Center, Meizhou, Guangdong Province, 514021 China

[Abstract] Objective To discuss 5,10-Polymorphisms of C677T, A1298C, and A66G of the methionine synthase reductase (MTRR) gene in the methylenetetrahydrofolate reductase (MTHFR) gene were associated with unexplained recurrent abortion. Methods A case-case-control study was adopted. 130 patients with unexplained fetal discontinuations of ≥ 2 visits to the reproductive center of our hospital from July 2017 to July 2019 were selected as the case group, and 122 patients with gestational age greater than 28 weeks, uncomplicated pregnant women or women with more than one child who have not had an abortion were used as the control group. Genotypes were compared between the case group and the control group, and the polymorphism of MTHFR gene C677T, A1298C and MTRR gene A66G were analyzed. Results At the C677T locus of the MTHFR gene, the CC gene frequency in the case group was 30.77%, the CC gene frequency in the control group was 57.38%, the difference was statistically significant(χ2=18.115,P<0.05); the CT gene frequency in the case group was 55.38%, and the CT gene frequency in the control group was 37.70%, the difference was statistically significant(χ2=7.900,P<0.05); case group TT gene frequency was 13.85%, control group TT gene frequency was 4.92%, the difference was statistically significant(χ2=5.821,P<0.05); case group C allele frequency was 58.46%, control group C of allele frequency was 76.23%, the difference was statistically significant(χ2=32.389,P<0.05); the T allele frequency in the case group was 41.54%, and the T allele frequency in the control group was 23.77%, the difference was statistically significant(χ2=32.389,P<0.05). The differences in the distribution of CC, CT, and TT genotypes, C alleles, and T alleles between the two groups of patients were statistically significant (P<0.05). There was no significant difference between MTHFR gene A1298C locus and MTRR gene A66G loci polymorphism case group and control group (P>0.05). Conclusion Unexplained recurrent miscarriage is related to the MTHFR gene C677T polymorphism, and has no clear relationship with the MTHFR gene A1298C locus and MTRR gene A66G polymorphism.

该研究结果显示:MTHFR基因 C677T 位点中,病例组CC基因频率为30.77%,对照组CC基因频率为57.38%;病例组CT基因频率为55.38%,对照组CT基因频率为37.70%;病例组TT基因频率为13.85%,对照组TT基因频率为4.92%;病例组C等位基因频率为58.47%,对照组C等位基因频率为76.23%;病例组T等位基因频率为41.53%,对照组T等位基因频率为23.77%。两组患者在CC、CT、TT 3种基因型、C等位基因、T等位基因的分布差异有统计学意义(P<0.05)。MTHFR基因 A1298C位點、MTRR 基因A66G 位点多态性病例组和对照组差异无统计学意义(P>0.05)。

该次研究中,研究结果与Grechanina Yu等人[10]研究结果具有一致性,研究中指出,MTHFR基因 C677T 位点中,病例组CC基因频率为32.51%,对照组CC基因频率为56.39%;病例组CT基因频率为52.34%,对照组CT基因频率为30.34%;病例组TT基因频率为56.30%,对照组TT基因频率为4.39%;病例组C等位基因频率为56.20%,对照组C等位基因频率为80.45%;病例组T等位基因频率为43.12%,对照组T等位基因频率为20.13%。两组患者在CC、CT、TT3种基因型、C等位基因、T等位基因的分布差异有统计学意义(P<0.05)。

该次研究发现病例组习惯性流产患者与正常对照组之间MTHFR C677T位点较对照组明显升高,差异有统计学意义(P<0.05)。MTHFR基因 C677T位点多态性与复发性流产的发生有关。MTHFR基因 A1298C位点、MTRR 基因A66G 位点多态性病例组和对照组无明显差异,考虑MTHFR基因 A1298C位点、MTRR 基因A66G 位点多态性与复发性流产无明确关系。

目前妇女在围孕期通过增补叶酸的方式可有效避免胎儿NTD的出现,但一些研究[11]也认为,围孕期增补叶酸还有可能预防其他出生缺陷,如先天性心脏病、泌尿系统畸形、肢体短缩畸形、唇腭裂等。目前,我国也推行围孕期0.4 mg/d叶酸补充的方案。但对于MTHFR、 MTRR基因突变等复杂原因导致的RSA患者,通过补充叶酸以及叶酸用药剂量以及用药周期等是否真正具有预防血栓效果以及实际治疗方案还不明确[12]。该研究通过对MTHFR、MTRR 基因多态性的患者孕前3个月及妊娠期补充0.8 mg叶酸或者含0.8 mg叶酸的复合维生素,观察其再次妊娠后的妊娠结局情况,其中早期流产率为13.04%,流产率稍降低。补充叶酸能够使同型半胱氨酸水平明显降低,从而降低了流产率,但由于该研究对复发性流产患者的年龄以及应用其他安胎治疗方式等未做全部的统计,不能完全判断是每天补充0.8 mg叶酸一定能治疗MTRR 基因A66G 位点以及MTHFR基因C677T位点、A1298C位点多态性造成的不明原因复发性流产,因此需要更多的研究来证明补充叶酸的时间和补充叶酸的剂量。

[参考文献]

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[10]  Grechanina Yu,Bugaeva E,Lisniak S,et al. Successful Rehabilitation of Patient Disabled by the Autistic Spectrum Disorder and the Modififd Epigenetic Status (Polymorphisms Drd2 2137 T/T, Mtrr 66 A/G, Mthfr 677 C/T, Mthfr 1298 A/C)-Case Report[J].Georgian medical news,2019(290):124-127.

[11]  赵雪杰,李晓娜,孙茗,等.叶酸代谢相关酶MTHFR、MTRR基因多态性与不良孕产史的关系[J].检验医学与临床,2019, 16(19):2761-2763.

(收稿日期:2020-03-01)

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