Association between Methylenetetrahydrofolate Reductase Gene Polymorphism and the Risk of Unexplained Recurrent Spontaneous Abortion: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 MIMan-li ¹ , SONGYan-xin ¹ , AIHai-quan ² ,  LAXiao-lin ²

1. Luoyang Women and Children Medical Care Center, Luoyang 471000, China;
2. Department of Reproductive Medicine Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China;

Corresponding?author：

LAXiao-lin, Email: xiaolinla@hotmail.com

Keywords：

Methylenetetrahydrofolate reductase; Gene polymorphism; Unexplained recurrent spontaneous abortion; Meta-analysis

DOI：

10.7507/1672-2531.20160139

Video：

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Objective To systematically review the association between C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and the risk of unexplained recurrent spontaneous abortion (URSA). Methods We searched PubMed, EMbase, CBM, CNKI, VIP and WanFang Data from inception to May 2015 to collect case-control studies about the association between the MTHFR gene C677T and A1298C polymorphisms and the risk of URSA. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.0 and Stata 12.0 software. Results A total of 42 case-control studies involving 3 970 URSA patients and 5 297 controls were included. The results of meta-analysis showed that MTHFR C677T polymorphism was associated with the increased risk of URSA (T vs. C: OR=1.34, 95% CI 1.16 to1.54, P < 0.000 01; TT vs. TC+CC: OR=1.70, 95% CI 1.36 to 2.12, P < 0.000 01; TT+TC vs. CC: OR=1.34, 95% CI 1.11 to 1.62, P=0.002; TC vs. CC: OR=1.19, 95% CI 0.99 to 1.43, P=0.061; TT vs. CC: OR=1.95, 95% CI 1.48 to 2.56, P < 0.000 01). Subgroup analysis by ethnicity indicated that the MTHFR C677T polymorphism was associated with the increased risk of URSA in east Asians (T vs. C: OR=1.61, 95% CI 1.39 to 1.87, P < 0.000 01; TT vs. TC+CC: OR=2.05, 95% CI 1.54 to 2.71, P < 0.000 01; TT+TC vs. CC: OR=1.76, 95% CI 1.41 to 2.19, P < 0.000 01; TC vs. CC: OR=1.53, 95% CI 1.21 to 1.94, P < 0.000 01; TT vs. CC: OR=2.77, 95% CI 1.94 to 3.97, P < 0.000 01) but was not associated with the increased risk of URSA in Caucasians. The results of meta-analysis also showed that there was no significant association between the MTHFR A1298C polymorphism and the URSA in all population. Conclusion Current evidence indicates that significant association is found between MTHFR C677T mutation and URSA in east Asians but not in Caucasians. Further study indicates that women carrying TT or TC gene significantly increases the risk of URSA and TT mutant gene carriers have a higher URSA risk. There is no significant association between MTHFR A1298C mutation and URSA in all population. Due to the quantity and quality limitations of included studies, more high quality case-control or cohort studies are needed to verify the above conclusions.

Citation： MIMan-li, SONGYan-xin, AIHai-quan, LAXiao-lin. Association between Methylenetetrahydrofolate Reductase Gene Polymorphism and the Risk of Unexplained Recurrent Spontaneous Abortion: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2016, 16(8): 897-905. doi: 10.7507/1672-2531.20160139 Copy

1.	?Stirrat GM. Recurrent miscarriage. Lancet, 1990, 336(8716):673-675.
2.	Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet, 2005, 272(2):95-108.
3.	Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet, 339(8801):1122-1123.
4.	Lissak A, Sharon A, Frnehters O, et al. Polymorphism for mutation of cytocine to thymine at location 677 in the methylenetetrahydrofolate reduetase gene is associate with recurrent early fetal loss. Am J Obstet Gynecol, 1999, 18l(1):126-130.
5.	劉宇巖, 楊博逸, 李永芳, 等. 5, 10-亞甲基四氫葉酸還原酶C677T基因多態性與原因不明復發性流產關聯的Meta分析.中國全科醫學, 2013, 16(31):2992-2997.
6.	曾憲濤, 劉慧, 陳曦, 等. Meta分析系列之四:觀察性研究的質量評價工具.中國循證心血管醫學雜志, 2012, 4(4):297-299.
7.	Bae J, Choi DH, Kang MS, et al. Effect of methylenetetrahydrofolate reductase and thymidylate synthase enhancer region polymorphisms on the risk of idiopathic recurrent spontaneous abortion in a Korean population. Fertil Steril, 2009, 91(4 Suppl):1560-1562.
8.	Ciacci C, Tortora R, Scudiero O, et al. Early pregnancy loss in celiac women:The role of genetic markers of thrombophilia. Dig Liver Dis, 2009, 41(10):717-720.
9.	Couto E, Barini R, Zaccaria R, et al. Association of anticardiolipin antibody and C677T in methylenetetrahydrofolate reductase mutation in women with recurrent spontaneous abortions:a new path to thrombophilia. Sao Paulo Med J, 2005, 123(1):15-20.
10.	Dilley A, Benito C, Hooper WC, et al. Mutations in the factor V, prothrombin and MTHFR genes are not risk factors for recurrent fetal loss. J Matern Fetal Neonatal Med, 2002, 11(3):176-182.
11.	Grandone E, Margaglione M, Colaizzo D, et al. Methylene tetrahydrofolate reductase (MTHFR) 677T>C mutation and unexplained early pregnancy loss. Thromb Haemost, 1998, 79(5): 1056-1057.
12.	Hohlagschwandtner M, Unfried G, Heinze G, et al. Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage. Fertil Steril, 2003, 79(5):1141-1148.
13.	Holmes ZR, Regan L, Chilcott I, et al. The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss. Br J Haematol, 1999, 105(1):98-101.
14.	Kim SY, Park SY, Choi JW, et al. Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy. Am J Reprod Immunol, 2011, 66(4):252-258.
15.	Kobashi G, Kato EH, Morikawa M, et al. MTHFR C677T Polymorphism and factor V Leiden mutation are not associated with recurrent spontaneous abortion of unexplained etiology in Japanese women. Semin Thromb Hemost, 2005, 31(3):266-271.
16.	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 Obstet Gynaecol, 2003, 23(1):55-58.
17.	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. Reprod Sci, 2014, 22(7):845-851.
18.	Lissak A, Sharon A, Fruchter O, et al. Polymorphism for mutation of cytosine to thymine at location 677 in the methylenetetrahydrofolate reductase gene is associated with recurrent early fetal loss. Am J Obstet Gynecol, 1999, 181(1):126-130.
19.	Makino A, Nakanishi T, Sugiura-Ogasawara M, et al. No association of C677T methylenetetrahydrofolate reductase and an endothelial nitric oxide synthase polymorphism with recurrent pregnancy loss. Am J Reprod Immunol, 2004, 52(1):60-66.
20.	Mtiraoui N, Zammiti W, Ghazouani L, et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Reproduction, 2006, 131(2):395-401.
21.	Murphy RP, Donoghue C, Nallen RJ, et al. Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy. Arterioscler Thromb Vasc Biol, 2000, 20(1):266-270.
22.	Nair RR, Khanna A, Singh K. MTHFR C677T polymorphism and recurrent early pregnancy loss risk in north Indian population. Reprod Sci, 2012, 19(2):210-215.
23.	Nelen WL, Steegers EA, Eskes TK, et al. Genetic risk factor for unexplained recurrent early pregnancy loss. Lancet, 1997, 350(9081): 861.
24.	Parle-McDermott A, Pangilinan F, Mills JL, et al. A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod, 2005, 11(7):477-480.
25.	Pauer HU, Voigt-Tschirschwitz T, Hinney B, et al. Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand, 2003, 82(10):942-947.
26.	Pihusch R, Buchholz T, Lohse P, et al. Thrombophilic gene mutations and recurrent spontaneous abortion:prothrombin mutation increases the risk in the first trimester. Am J Reprod Immunol, 2001, 46(2):124-131.
27.	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 Perinat Med, 2013, 41(5):549-554.
28.	Settin A, Elshazli R, Salama A, et al. Methylenetetrahydrofolate reductase gene olymorphisms in Egyptian women with unexplained recurrent pregnancy loss. Genet Test Mol Biomarkers, 2011, 15(12): 887-892.
29.	Sotiriadis A, Vartholomatos G, Pavlou M, et al. Combined thrombophilic mutations in women with unexplained recurrent miscarriage. Am J Reprod Immunol, 2007, 57(2):133-141.
30.	Toth B, Vocke F, Rogenhofer N, et al. Paternal thrombophilic gene mutations are not associated with recurrent miscarriage. Am J Reprod Immunol, 2008, 60(4):325-332.
31.	Unfried G, Griesmacher A, Weismüller W, et al. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage. Obstet Gynecol, 2002, 99(4):614-619.
32.	Vanilla S, Dayanand CD, Kotur PF, et al. Evidence of Paternal N5, N10-Methylenetetrahydrofolate Reductase (MTHFR) C677T Gene Polymorphism in Couples with Recurrent Spontaneous Abortions (RSAs) in Kolar District-A South West of India. Clin Diagn Res, 2015, 9(2):BC15-18.
33.	Vettriselvi V, Vijayalakshmi K, Paul SF, et al. ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss. J Obstet Gynaecol Res, 2008, 34(3):301-306.
34.	Wramsby ML, Sten-Linder M, Bremme K. Primary habitual abortions are associated with high frequency of factor V Leiden mutation. Fertil Steril, 2000, 74(5):987-991.
35.	萬加華, 劉肖曼, 張紅巖, 等.反復性自然流產患者MTHFR基因的多態性研究.中國與遺傳雜志, 2007, 15(7):9-10.
36.	宋綠茵, 戚潛輝, 余達賢, 等.同型半胱氨酸代謝相關酶基因多態性與習慣性流產關系的研究.中華圍產醫學雜, 2005, 8(3):160-164.
37.	徐俐, 劉肖曼, 張紅巖, 等.亞甲基四氫葉酸還原酶、凝血因子V和凝血酶原基因多態性與原因不明復發性早期流產的關系.中華婦產科雜志, 2007, 42(3):180-183.
38.	李曉梅, 張友忠, 許燕雪, 等. MTHFR基因C677T位點多態性與不明原因重復性自然流產的相關性.中華醫學遺傳學雜志, 2004, 21(1):39-42.
39.	汪希鵬, 林其德, 馬政文, 等.原因不明復發性流產患者血中亞甲基四氫葉酸還原酶基因C677T和A1298C位點突變的研究.中華婦產科雜志, 2004, 39(4):238-241.
40.	王亞文, 李芬, 李義平, 等.亞甲基四氫葉酸還原酶677C→T突變與不明原因反復流產相關性研究.中國實用婦科與產科志, 2002, 18(5):291-293.
41.	王蘇梅, 賈頤舫, 楊丹形, 等. MTHFR基因C677T多態性與原因不明復發性自然流產的相關性.中國婦幼保健, 2011, 26(9):1385-1387.
42.	管立學, 杜欣瑩, 王敬先, 等. PAI-1基因和MTHFR基因多態性與復發性早期自然流產的關系.中華醫學遺傳學雜志, 2005, 22(3): 330-333.
43.	胡曉東, 梁佩燕, 刁梁輝, 等.亞甲基四氫葉酸還原酶基因突變不明原因復發性流產的關系.中國優生與遺傳雜志, 2014, 22(11):87-89.
44.	董素芹, 杜欣瑩, 劉學云. MTHFR基因多態性與不明原因習慣性流產的相關性分析.實用婦產科雜志, 2006, 22(8):500-501.
45.	鐘慧軍, 劉軍紅, 朱永生, 等. MTHFR C677T基因多態性與復發性自然流產的相關性研究.寧夏醫學雜志, 2010, 32(8):675-676.
46.	陳惠麗, 唐落韻, 陳春寶, 等.不明原因復發性流產與亞甲基四氫葉酸還原酶及甲硫氨酸合成酶還原酶基因多態性研究.中國優生與遺傳雜志, 2013, 21(6):29-30.
47.	韓紅敬, 沈浣, 王艷檳, 等.亞甲基四氫葉酸還原酶基因677位多態性、高同型半胱氨酸血癥與復發性流產.生殖與避孕, 2012, 32(7):486-489.
48.	馬淑芳, 鄭梅玲. MTHFR C677T基因多態性及血漿HCY與復發性流產的關系.中國優生優育, 2009, 15(1):12-13, 16.
49.	Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reductase:isolation of cDNA, mapping and mutation identification. Nat Genet, 1994, 7(2):195-200.
50.	Unfried G, Griesmacher A, Weismüller W, et al. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage. Obstet Gynecol, 2002, 99(4):614-619.
51.	Ananth CV, Peltier MR, De Marco C, et al. Associations between 2 polymorphisms in the methylenetetrahydrofolate reductase gene and placental abruption. Am J Obstet Gynecol, 2007, 197(4):385-387.
52.	王蘇梅, 邱毅, 高雪芹, 等.亞甲基四氫葉酸還原酶基因多態性與妊娠相關疾病.國外醫學(婦產科學分冊), 2004, 31(5):303-305.
53.	Zetterberg H, Regland B, Palmér M, et al. Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated al/eles in spontaneously aborted embryos. Eur J Hum Genet, 2002, 10(2):113-118.

1. ?Stirrat GM. Recurrent miscarriage. Lancet, 1990, 336(8716):673-675.
2. Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet, 2005, 272(2):95-108.
3. Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet, 339(8801):1122-1123.
4. Lissak A, Sharon A, Frnehters O, et al. Polymorphism for mutation of cytocine to thymine at location 677 in the methylenetetrahydrofolate reduetase gene is associate with recurrent early fetal loss. Am J Obstet Gynecol, 1999, 18l(1):126-130.
5. 劉宇巖, 楊博逸, 李永芳, 等. 5, 10-亞甲基四氫葉酸還原酶C677T基因多態性與原因不明復發性流產關聯的Meta分析.中國全科醫學, 2013, 16(31):2992-2997.
6. 曾憲濤, 劉慧, 陳曦, 等. Meta分析系列之四:觀察性研究的質量評價工具.中國循證心血管醫學雜志, 2012, 4(4):297-299.
7. Bae J, Choi DH, Kang MS, et al. Effect of methylenetetrahydrofolate reductase and thymidylate synthase enhancer region polymorphisms on the risk of idiopathic recurrent spontaneous abortion in a Korean population. Fertil Steril, 2009, 91(4 Suppl):1560-1562.
8. Ciacci C, Tortora R, Scudiero O, et al. Early pregnancy loss in celiac women:The role of genetic markers of thrombophilia. Dig Liver Dis, 2009, 41(10):717-720.
9. Couto E, Barini R, Zaccaria R, et al. Association of anticardiolipin antibody and C677T in methylenetetrahydrofolate reductase mutation in women with recurrent spontaneous abortions:a new path to thrombophilia. Sao Paulo Med J, 2005, 123(1):15-20.
10. Dilley A, Benito C, Hooper WC, et al. Mutations in the factor V, prothrombin and MTHFR genes are not risk factors for recurrent fetal loss. J Matern Fetal Neonatal Med, 2002, 11(3):176-182.
11. Grandone E, Margaglione M, Colaizzo D, et al. Methylene tetrahydrofolate reductase (MTHFR) 677T>C mutation and unexplained early pregnancy loss. Thromb Haemost, 1998, 79(5): 1056-1057.
12. Hohlagschwandtner M, Unfried G, Heinze G, et al. Combined thrombophilic polymorphisms in women with idiopathic recurrent miscarriage. Fertil Steril, 2003, 79(5):1141-1148.
13. Holmes ZR, Regan L, Chilcott I, et al. The C677T MTHFR gene mutation is not predictive of risk for recurrent fetal loss. Br J Haematol, 1999, 105(1):98-101.
14. Kim SY, Park SY, Choi JW, et al. Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy. Am J Reprod Immunol, 2011, 66(4):252-258.
15. Kobashi G, Kato EH, Morikawa M, et al. MTHFR C677T Polymorphism and factor V Leiden mutation are not associated with recurrent spontaneous abortion of unexplained etiology in Japanese women. Semin Thromb Hemost, 2005, 31(3):266-271.
16. 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 Obstet Gynaecol, 2003, 23(1):55-58.
17. 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. Reprod Sci, 2014, 22(7):845-851.
18. Lissak A, Sharon A, Fruchter O, et al. Polymorphism for mutation of cytosine to thymine at location 677 in the methylenetetrahydrofolate reductase gene is associated with recurrent early fetal loss. Am J Obstet Gynecol, 1999, 181(1):126-130.
19. Makino A, Nakanishi T, Sugiura-Ogasawara M, et al. No association of C677T methylenetetrahydrofolate reductase and an endothelial nitric oxide synthase polymorphism with recurrent pregnancy loss. Am J Reprod Immunol, 2004, 52(1):60-66.
20. Mtiraoui N, Zammiti W, Ghazouani L, et al. Methylenetetrahydrofolate reductase C677T and A1298C polymorphism and changes in homocysteine concentrations in women with idiopathic recurrent pregnancy losses. Reproduction, 2006, 131(2):395-401.
21. Murphy RP, Donoghue C, Nallen RJ, et al. Prospective evaluation of the risk conferred by factor V Leiden and thermolabile methylenetetrahydrofolate reductase polymorphisms in pregnancy. Arterioscler Thromb Vasc Biol, 2000, 20(1):266-270.
22. Nair RR, Khanna A, Singh K. MTHFR C677T polymorphism and recurrent early pregnancy loss risk in north Indian population. Reprod Sci, 2012, 19(2):210-215.
23. Nelen WL, Steegers EA, Eskes TK, et al. Genetic risk factor for unexplained recurrent early pregnancy loss. Lancet, 1997, 350(9081): 861.
24. Parle-McDermott A, Pangilinan F, Mills JL, et al. A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss. Mol Hum Reprod, 2005, 11(7):477-480.
25. Pauer HU, Voigt-Tschirschwitz T, Hinney B, et al. Analyzes of three common thrombophilic gene mutations in German women with recurrent abortions. Acta Obstet Gynecol Scand, 2003, 82(10):942-947.
26. Pihusch R, Buchholz T, Lohse P, et al. Thrombophilic gene mutations and recurrent spontaneous abortion:prothrombin mutation increases the risk in the first trimester. Am J Reprod Immunol, 2001, 46(2):124-131.
27. 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 Perinat Med, 2013, 41(5):549-554.
28. Settin A, Elshazli R, Salama A, et al. Methylenetetrahydrofolate reductase gene olymorphisms in Egyptian women with unexplained recurrent pregnancy loss. Genet Test Mol Biomarkers, 2011, 15(12): 887-892.
29. Sotiriadis A, Vartholomatos G, Pavlou M, et al. Combined thrombophilic mutations in women with unexplained recurrent miscarriage. Am J Reprod Immunol, 2007, 57(2):133-141.
30. Toth B, Vocke F, Rogenhofer N, et al. Paternal thrombophilic gene mutations are not associated with recurrent miscarriage. Am J Reprod Immunol, 2008, 60(4):325-332.
31. Unfried G, Griesmacher A, Weismüller W, et al. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage. Obstet Gynecol, 2002, 99(4):614-619.
32. Vanilla S, Dayanand CD, Kotur PF, et al. Evidence of Paternal N5, N10-Methylenetetrahydrofolate Reductase (MTHFR) C677T Gene Polymorphism in Couples with Recurrent Spontaneous Abortions (RSAs) in Kolar District-A South West of India. Clin Diagn Res, 2015, 9(2):BC15-18.
33. Vettriselvi V, Vijayalakshmi K, Paul SF, et al. ACE and MTHFR gene polymorphisms in unexplained recurrent pregnancy loss. J Obstet Gynaecol Res, 2008, 34(3):301-306.
34. Wramsby ML, Sten-Linder M, Bremme K. Primary habitual abortions are associated with high frequency of factor V Leiden mutation. Fertil Steril, 2000, 74(5):987-991.
35. 萬加華, 劉肖曼, 張紅巖, 等.反復性自然流產患者MTHFR基因的多態性研究.中國與遺傳雜志, 2007, 15(7):9-10.
36. 宋綠茵, 戚潛輝, 余達賢, 等.同型半胱氨酸代謝相關酶基因多態性與習慣性流產關系的研究.中華圍產醫學雜, 2005, 8(3):160-164.
37. 徐俐, 劉肖曼, 張紅巖, 等.亞甲基四氫葉酸還原酶、凝血因子V和凝血酶原基因多態性與原因不明復發性早期流產的關系.中華婦產科雜志, 2007, 42(3):180-183.
38. 李曉梅, 張友忠, 許燕雪, 等. MTHFR基因C677T位點多態性與不明原因重復性自然流產的相關性.中華醫學遺傳學雜志, 2004, 21(1):39-42.
39. 汪希鵬, 林其德, 馬政文, 等.原因不明復發性流產患者血中亞甲基四氫葉酸還原酶基因C677T和A1298C位點突變的研究.中華婦產科雜志, 2004, 39(4):238-241.
40. 王亞文, 李芬, 李義平, 等.亞甲基四氫葉酸還原酶677C→T突變與不明原因反復流產相關性研究.中國實用婦科與產科志, 2002, 18(5):291-293.
41. 王蘇梅, 賈頤舫, 楊丹形, 等. MTHFR基因C677T多態性與原因不明復發性自然流產的相關性.中國婦幼保健, 2011, 26(9):1385-1387.
42. 管立學, 杜欣瑩, 王敬先, 等. PAI-1基因和MTHFR基因多態性與復發性早期自然流產的關系.中華醫學遺傳學雜志, 2005, 22(3): 330-333.
43. 胡曉東, 梁佩燕, 刁梁輝, 等.亞甲基四氫葉酸還原酶基因突變不明原因復發性流產的關系.中國優生與遺傳雜志, 2014, 22(11):87-89.
44. 董素芹, 杜欣瑩, 劉學云. MTHFR基因多態性與不明原因習慣性流產的相關性分析.實用婦產科雜志, 2006, 22(8):500-501.
45. 鐘慧軍, 劉軍紅, 朱永生, 等. MTHFR C677T基因多態性與復發性自然流產的相關性研究.寧夏醫學雜志, 2010, 32(8):675-676.
46. 陳惠麗, 唐落韻, 陳春寶, 等.不明原因復發性流產與亞甲基四氫葉酸還原酶及甲硫氨酸合成酶還原酶基因多態性研究.中國優生與遺傳雜志, 2013, 21(6):29-30.
47. 韓紅敬, 沈浣, 王艷檳, 等.亞甲基四氫葉酸還原酶基因677位多態性、高同型半胱氨酸血癥與復發性流產.生殖與避孕, 2012, 32(7):486-489.
48. 馬淑芳, 鄭梅玲. MTHFR C677T基因多態性及血漿HCY與復發性流產的關系.中國優生優育, 2009, 15(1):12-13, 16.
49. Goyette P, Sumner JS, Milos R, et al. Human methylenetetrahydrofolate reductase:isolation of cDNA, mapping and mutation identification. Nat Genet, 1994, 7(2):195-200.
50. Unfried G, Griesmacher A, Weismüller W, et al. The C677T polymorphism of the methylenetetrahydrofolate reductase gene and idiopathic recurrent miscarriage. Obstet Gynecol, 2002, 99(4):614-619.
51. Ananth CV, Peltier MR, De Marco C, et al. Associations between 2 polymorphisms in the methylenetetrahydrofolate reductase gene and placental abruption. Am J Obstet Gynecol, 2007, 197(4):385-387.
52. 王蘇梅, 邱毅, 高雪芹, 等.亞甲基四氫葉酸還原酶基因多態性與妊娠相關疾病.國外醫學(婦產科學分冊), 2004, 31(5):303-305.
53. Zetterberg H, Regland B, Palmér M, et al. Increased frequency of combined methylenetetrahydrofolate reductase C677T and A1298C mutated al/eles in spontaneously aborted embryos. Eur J Hum Genet, 2002, 10(2):113-118.

Chinese Journal of Evidence-Based Medicine

Association between Methylenetetrahydrofolate Reductase Gene Polymorphism and the Risk of Unexplained Recurrent Spontaneous Abortion: A Meta-analysis

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