母胎亚甲基四氢叶酸还原酶基因C677T多态性与不明原因习惯性流产发生风险的相关性研究
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摘要
目的探讨母亲和胎儿亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与不明原因习惯性流产的相关性。方法选取100例不明原因习惯性流产史的患者为病例组,同时收集70例病例组中流产胎儿组织样本;另征集100例正常妊娠者作为对照,其中70例有胎儿脐带血。采用PCR-芯片杂交法检测病例组、对照组以及流产胎儿组织、脐带血的MTHFR C677T基因多态性,统计学分析不同基因型孕妇、胎儿与不明原因习惯性流产风险的相关性。结果对照组C/C基因型频率显著高于病例组C/C基因型频率(35.0%vs.18.0%)(P<0.05),两组C/T基因型频率比较无显著性差异(P>0.05),病例组T/T基因型频率显著高于对照组T/T基因型频率(38.0%vs.24.0%)(P<0.05);与对照组相比,病例组等位基因C频率(40.0%vs.55.5%)显著降低,而等位基因T频率(60.0%vs.45.5%)显著升高,差异具有统计学意义(P<0.05);病例组与对照组配对的母亲-胎儿同时携带MTHFR677位T等位基因比较,频率显著升高(74.3%vs.52.9%),差异有统计学意义(P<0.05)。结论 MTHFRC677T基因型多态性是不明原因习惯性流产风险因子之一,若母婴同时携带T等位基因,不明原因习惯性流产风险进一步升高。
Objective:To investigate the association between MTHFR polymorphism C677 Tand unexplained recurrent spontaneous abortion.Methods: A hundred patients with unexplained recurrent spontaneous abortion were selected as case group,and 70 samples of abortion fetal tissues were collected.Another 100 healthy women with normal pregnancy history served as control group,and 70 samples of fetal umbilical cord blood were collected.PCR-chip hybridization was applied to detect the MTHFR gene C677 T polymorphism.The correlation between MTHFR polymorphism and the risk of unexplained recurrent spontaneous abortion was analyzed based on different genotype groups.Results:The incidence of C/C genotype in the control group was significantly higher than that in the case group(35.0% vs.18.0%)(P<0.05).There was no significant difference in the incidence of C/T genotype between the two groups(P>0.05).The incidence of genotype T/T genotype in case group weresignificantly higher than that in the control group(38.0% vs.24.0%)(P<0.05).Compared with the control group,the incidence of allele C was significantly lower(40.0% vs.55.5%),but the incidence of allele T was significantly higher(60.0% vs.45.5%)in case group(P<0.05).There was also significant difference in the incidence of both mother and fetus carrying T allele between the case group and the control group(74.3% vs.52.9%)(P<0.05).Conclusions: MTHFR C677 T polymorphism is related with the risk of unexplained recurrent spontaneous abortion.Furthermore,both mother and fetus carrying T allele enhances the risk of unexplained recurrent spontaneous abortion.
Objective:To investigate the association between MTHFR polymorphism C677 Tand unexplained recurrent spontaneous abortion.Methods: A hundred patients with unexplained recurrent spontaneous abortion were selected as case group,and 70 samples of abortion fetal tissues were collected.Another 100 healthy women with normal pregnancy history served as control group,and 70 samples of fetal umbilical cord blood were collected.PCR-chip hybridization was applied to detect the MTHFR gene C677 T polymorphism.The correlation between MTHFR polymorphism and the risk of unexplained recurrent spontaneous abortion was analyzed based on different genotype groups.Results:The incidence of C/C genotype in the control group was significantly higher than that in the case group(35.0% vs.18.0%)(P<0.05).There was no significant difference in the incidence of C/T genotype between the two groups(P>0.05).The incidence of genotype T/T genotype in case group weresignificantly higher than that in the control group(38.0% vs.24.0%)(P<0.05).Compared with the control group,the incidence of allele C was significantly lower(40.0% vs.55.5%),but the incidence of allele T was significantly higher(60.0% vs.45.5%)in case group(P<0.05).There was also significant difference in the incidence of both mother and fetus carrying T allele between the case group and the control group(74.3% vs.52.9%)(P<0.05).Conclusions: MTHFR C677 T polymorphism is related with the risk of unexplained recurrent spontaneous abortion.Furthermore,both mother and fetus carrying T allele enhances the risk of unexplained recurrent spontaneous abortion.
引文
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[13]Cao Y,Xu J,Zhang Z,et al.Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss:a meta-analysis[J].Gene,2013,514:105-111.
[14]Luo L,Chen Y,Wang L,et al.Polymorphisms of genes involved in the folate metabolic pathway impact the occurrence of unexplained recurrent pregnancy loss[J].Reprod Sci,2015,22:845-851.
[15]Spiroski I,Kedev S,Antov S,et al.Methylenetetrahydrofb late reductase(MTHFR-677and MTHFR-1298)genotypes and and haplotypes and plasma homoeystine levels in patients with occlusive artery disease and deep venous thrombosis[J].Acta biochimpol,2008,55:587-594.
[16]毛仁芳,范义辉,白静,等.亚甲基四氨叶酸还原酶基因多态性及其与疾病的关系[J].国际遗传学杂志,2007,30:39-43.
[17]Nelen WL,Blom HJ,Steegers EA,et al.Homocysteine and folate levels as risk factors for recurrent early pregnancy loss[J].Obstet Gynecol,2000,95:519-524.
[18]Boot,Steegers-Theunissen RP,Poolmann RE,et al.Cardiac outflow tract malfbrmations in chick embroys exposed to homcysteine[J].Cardiovasc Res,2004,64:365-373.
[19]Nadir Y,Hoffman R,Brenner B.Association of homocysteine,vitamin B12,folic acid,and MTHFR C677Tin patients with a thrombotic event or recurrent fetal loss[J].Ann Hematol,2007,86:35-40.
[20]Alomari MA,Khabour OF,Gharaibeh MY,et al.Effect of physical activity on levels of homocysteine,folate,and vitamin B12in the elderly[J].Phys Sportsmed,2016,44:68-73.
[21]Liu B,Ma S,Wang T,et al.A novel rat model of heart failure induced by high methionine diet showing evidence of association between hyperhomocysteinemia and activation of NF-kappaB[J].Am J Transl Res,2016,8:117-124.
[22]王亚文,李芬,李义平,等.夫妻配对MTHFR基因型分布与不明原因反复流产的关系[J].西安交通大学学报(医学版),2002,23:357-359.
[23]顾莹,杨舒婷,汤欣欣,等.不明原因复发性自然流产夫妇MTHFR C677T位点多态性分析[J].现代生物医学进展,2015,15:5244-5247.
[2]Eltayeb SM,Ambusaidi SK,Gowri V,et al.Etiological profile of Omani women with recurrent pregnancy loss[J].Saudi Med J,2014,35:757-760.
[3]Mumusoglu S,Beksac MS,Ekiz A,et al.Does the presence of autoantibodies without autoimmune diseases and hereditary thrombophilia have an effect on recurrent pregnancy loss?[J].J Matern Fetal Neonatal Med,2016,29:2352-2357.
[4]陈红燕,黎欧阳,庞丽红,等.复发性流产病人绒毛组织中FK506结合蛋白52的表达及意义[J].中国实用妇科与产科杂志,2015,31:632-635.
[5]Sherkat R,Meidani M,Zarabian H,et al.Seropositivity of cytomegalovirus in patients with recurrent pregnancy loss[J].J Res Med Sci,2014,19:S22-25.
[6]Pluchino N,Drakopoulos P,Wenger JM,et al.Hormonal causes of recurrent pregnancy loss(RPL)[J].Hormones(Athens),2014,13:314-322.
[7]Ford HB,Schust DJ.Recurrent pregnancy loss:etiology,diagnosis,and therapy[J].Rev Obstet Gynecol,2009,2:76-83.
[8]Saravelos SH,Regan L.Unexplained recurrent pregnancy loss[J].Obstet Gynecol Clin North Am,2014,41:157-166.
[9]韩红敬,沈浣,王艳槟,等.亚甲基四氢叶酸还原酶基因677位多态性、高同型半胱氨酸血症与复发性流产[J].生殖与避孕,2012,32:486-489,477.
[10]Coriu L,Copaciu E,Tulbure D,et al.Inherited thrombophilia in pregnant women with intrauterine growth restriction[J].Maedica(Buchar),2014,9:351-355.
[11]肖世金,赵爱民.复发性流产的病因学研究进展[J].中国实用妇科与产科杂志,2014,30:41-45.
[12]Zetterberg H,Regland B,Palmer M,et al.Increased frequency of combined methylenetetrahydrofolate reductase C677Tand A1298Cmutated alleles in spontaneously aborted embryos[J].Eur J Hum Genet,2002,10:113-118.
[13]Cao Y,Xu J,Zhang Z,et al.Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss:a meta-analysis[J].Gene,2013,514:105-111.
[14]Luo L,Chen Y,Wang L,et al.Polymorphisms of genes involved in the folate metabolic pathway impact the occurrence of unexplained recurrent pregnancy loss[J].Reprod Sci,2015,22:845-851.
[15]Spiroski I,Kedev S,Antov S,et al.Methylenetetrahydrofb late reductase(MTHFR-677and MTHFR-1298)genotypes and and haplotypes and plasma homoeystine levels in patients with occlusive artery disease and deep venous thrombosis[J].Acta biochimpol,2008,55:587-594.
[16]毛仁芳,范义辉,白静,等.亚甲基四氨叶酸还原酶基因多态性及其与疾病的关系[J].国际遗传学杂志,2007,30:39-43.
[17]Nelen WL,Blom HJ,Steegers EA,et al.Homocysteine and folate levels as risk factors for recurrent early pregnancy loss[J].Obstet Gynecol,2000,95:519-524.
[18]Boot,Steegers-Theunissen RP,Poolmann RE,et al.Cardiac outflow tract malfbrmations in chick embroys exposed to homcysteine[J].Cardiovasc Res,2004,64:365-373.
[19]Nadir Y,Hoffman R,Brenner B.Association of homocysteine,vitamin B12,folic acid,and MTHFR C677Tin patients with a thrombotic event or recurrent fetal loss[J].Ann Hematol,2007,86:35-40.
[20]Alomari MA,Khabour OF,Gharaibeh MY,et al.Effect of physical activity on levels of homocysteine,folate,and vitamin B12in the elderly[J].Phys Sportsmed,2016,44:68-73.
[21]Liu B,Ma S,Wang T,et al.A novel rat model of heart failure induced by high methionine diet showing evidence of association between hyperhomocysteinemia and activation of NF-kappaB[J].Am J Transl Res,2016,8:117-124.
[22]王亚文,李芬,李义平,等.夫妻配对MTHFR基因型分布与不明原因反复流产的关系[J].西安交通大学学报(医学版),2002,23:357-359.
[23]顾莹,杨舒婷,汤欣欣,等.不明原因复发性自然流产夫妇MTHFR C677T位点多态性分析[J].现代生物医学进展,2015,15:5244-5247.