Xiaoming Wu1, Lanjun Zhao, Hui Zhu, Dajian He, Wenru Tang, Ying Luo. 1. Lab of Molecular Genetics of Aging and Tumor, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China.
Abstract
BACKGROUND: C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with recurrent pregnancy loss (RPL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for MTHFR C677T polymorphism and RPL risk. METHODS: Electronic search of PubMed and the Chinese Biomedicine database was conducted to select studies. Case-control studies containing available genotype frequencies of C677T were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. RESULTS: The case-control studies including 2427 cases and 3118 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had increased risk of RPL (OR=1.574, 95% CI: 1.163-2.13, p=0.003), in Asians (OR=1.663, 95% CI: 1.012-2.731, p=0.045). Results among Caucasians did not suggest an association (OR=1.269, 95% CI: 0.914-1.761, p=0.155). A symmetric funnel plot, the Egger's test (p=0.285), and the Begg's test (p=0.529) were all suggestive of the lack of publication bias. The studies conducted in each of the defined number of pregnancy losses-two or more pregnancy losses, and three or more pregnancy losses-showed no effect of the C677T polymorphism on RPL except for the TT versus CT+CT genotype comparison for the three or more pregnancy loss subgroup (OR=1.792, 95% CI: 1.187-2.704, p=0.005). CONCLUSION: This meta-analysis supports the idea that MTHFR C677T genotype is associated with increased risk of RPL, except for Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between MTHFR C677T polymorphism and RPL.
BACKGROUND:C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) has been associated with recurrent pregnancy loss (RPL). However, results were conflicting. The aim of this study was to quantitatively summarize the evidence for MTHFRC677T polymorphism and RPL risk. METHODS: Electronic search of PubMed and the Chinese Biomedicine database was conducted to select studies. Case-control studies containing available genotype frequencies of C677T were chosen, and odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association. RESULTS: The case-control studies including 2427 cases and 3118 controls were identified. The meta-analysis stratified by ethnicity showed that individuals with the homozygous TT genotype had increased risk of RPL (OR=1.574, 95% CI: 1.163-2.13, p=0.003), in Asians (OR=1.663, 95% CI: 1.012-2.731, p=0.045). Results among Caucasians did not suggest an association (OR=1.269, 95% CI: 0.914-1.761, p=0.155). A symmetric funnel plot, the Egger's test (p=0.285), and the Begg's test (p=0.529) were all suggestive of the lack of publication bias. The studies conducted in each of the defined number of pregnancy losses-two or more pregnancy losses, and three or more pregnancy losses-showed no effect of the C677T polymorphism on RPL except for the TT versus CT+CT genotype comparison for the three or more pregnancy loss subgroup (OR=1.792, 95% CI: 1.187-2.704, p=0.005). CONCLUSION: This meta-analysis supports the idea that MTHFRC677T genotype is associated with increased risk of RPL, except for Caucasians. To draw comprehensive and true conclusions, further prospective studies with larger numbers of participants worldwide are needed to examine associations between MTHFRC677T polymorphism and RPL.
Authors: Catherine Igartua; Rachel A Myers; Rasika A Mathias; Maria Pino-Yanes; Celeste Eng; Penelope E Graves; Albert M Levin; Blanca E Del-Rio-Navarro; Daniel J Jackson; Oren E Livne; Nicholas Rafaels; Christopher K Edlund; James J Yang; Scott Huntsman; Muhammad T Salam; Isabelle Romieu; Raphael Mourad; James E Gern; Robert F Lemanske; Annah Wyss; Jane A Hoppin; Kathleen C Barnes; Esteban G Burchard; W James Gauderman; Fernando D Martinez; Benjamin A Raby; Scott T Weiss; L Keoki Williams; Stephanie J London; Frank D Gilliland; Dan L Nicolae; Carole Ober Journal: Nat Commun Date: 2015-01-16 Impact factor: 14.919