Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis
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Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses before the 20th week of gestation with the same partner. Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms were reported to have an effect on embryonic development and pregnancy success. To clarify the effects of MTHFR polymorphisms on the risk of RPL in the Chinese population, a meta-analysis was performed.
Materials and methods
Related studies were identified from Medline, Embase, Web of Science, and Chinese Databases up to March 7th, 2015. We extracted the number of both C677T and A1298C genotypes in the cases and controls. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to estimate the associations. Data analysis was performed using Stata 13.1.
Sixteen articles involving 1420 RPL cases and 1408 controls were included in this meta-analysis. MTHFR C677T polymorphism was significantly associated with RPL risk under dominant (TT + CT vs. CC; OR 2.10, 95 % CI 1.76–2.50), recessive (TT vs. CC + CT; OR 2.36, 95 % CI 1.92–2.90), heterozygote (CT vs. CC; OR 1.77, 95 % CI 1.32–2.37), homozygote (TT vs. CC; OR 3.55, 95 % CI 2.76–4.56), and additive (T vs. C; OR 1.83, 95 % CI 1.64–2.05) model. Sensitivity analyses excluding studies that deviated from HWE did not change the direction of effect. For the A1298C mutation, no significant association was found. The Egger’s regression asymmetry test showed no significant publication bias.
Identification of MTHFR C677T mutation would have some implication for primary prevention of RPL and screening of high-risk individuals in China. Large well-designed researches are needed to fully describe the associations.
KeywordsMethylenetetrahydrofolate reductase Recurrent pregnancy loss Meta-analysis Polymorphism
Compliance with ethical standards
The authors declare that there are no conflicts of interest.
- 5.Garrido-Gimenez C, Alijotas-Reig J (1073) Recurrent miscarriage: causes, evaluation and management. Postgrad Med J 2015(91):151–162Google Scholar
- 10.Kumar KS, Govindaiah V, Naushad SE, Devi RR, Jyothy A (2003) 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 23(1):55–58PubMedCrossRefGoogle Scholar
- 17.Wang Y, Li F, Li Y, Xue M, Yu X, Li X (2002) The study on the relationship between the methylenetetrahydrofolate reductase C677T mutation and unexplained recurrent pregnancy loss. Chin J Pract Gynecol Obstet 18(5):291–293Google Scholar
- 18.Song L, Qi Q, Tian G, She D, Zhang H (2003) Relationship between methylenetetrahydrofolate reductase gene mutations and recurrent spontaneous abortion. J Clin Med Bioeng 9(3):246–247Google Scholar
- 19.Li XM, Zhang YZ, Xu YX, Jiang S (2004) Study on the relationship of MTHFR polymorphisms with unexplained recurrent spontaneous abortion. Chin J Med Genet 21(1):39–42Google Scholar
- 20.Guan LX, Du XY, Wang JX et al (2005) Association of genetic polymorphisms in plasminogen activator inhibitor-1 gene and 5,10-methylenetetrahydrofolate reductase gene with recurrent early spontaneous abortion. Chin J Med Genet 22(3):330–333Google Scholar
- 22.Ren J, Han X, Liu X et al (2007) Methylenetetrahydrofolate reductase gene polymorphism in women with recurrent pregnancy loss. Chin J Perinat Med 10(2):80–84Google Scholar
- 23.Wan J, Liu X, Zhang H, Zhao J, Ma S (2007) Analyzes of susceptible gene in women with recurrent spontaneous abortions. Chin J Birth Health Hered 15(7):9–10Google Scholar
- 24.Xu L, Liu X, Zhang H, Zhao J, Qi Q, Chang Y (2007) Relationship between three thrombophilic gene mutations and unexplained recurrent early spontaneous abortion. Chin J Obstet Gynecol 42(3):180–183Google Scholar
- 25.Ma S, Zheng M (2008) The relation of MTHFRC677T gene polymorphism to recurrent abortion. Health Med Res Pract 5(4):4–5,9Google Scholar
- 26.Zhang JY, Zuo WJ, Wu GH, Sun HT (2009) Association between MTHFR gene C677T polymorphism and habitual abortion. J Jilin Univ Med Ed 35(4):698–701Google Scholar
- 27.Zhong H, Liu J, Zhu Y et al (2010) Study on correlation between MTHFR polymorphisms and repeated spontaneous abortion. J Ningxia Med 32(8):675–676Google Scholar
- 28.Wang S, Jia Y, Yang D et al (2011) Correlation between M THFR gene C677 T polymorphism and unexplained recurrent spontaneous abortion. Matern Child Health Care China 26(9):1385–1387Google Scholar
- 29.Han H, Shen H, Wang Y, Yu W (2012) Methylenetetrahydrofolate reductase C677T polymorphism and homocysteine in recurrent pregnancy loss. J Reprod Contracept 32(7):486–489, 477Google Scholar
- 30.Hu X, Liang P, Diao L et al (2014) The association of methylenetetrahydrofolate reductase gene mutation with unexplained recurrent miscarriage. Chin J Birth Health Hered 11:87–89Google Scholar
- 32.Wang S, Shi X, Shen R, Wang Q, Chen S, Zhang W (2009) The role of folate metabolism related enzymes gene polymorphisms on recurrent early spontaneous abortion. Chin J Birth Health Hered 17(3):12–13Google Scholar