Methylenetetrahydrofolate reductase C677T polymorphism and the risk of unexplained recurrent pregnancy loss: A meta-analysis

ObjectiveTo investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and the risk of unexplained recurrent pregnancy loss (URPL).DesignMeta-analysis of published case-control studies of the MTHFR C677T variant and URPL risk.SettingA research institution in China.Patient(s)Women with URPL.Intervention(s)None.Main Outcome Measure(s)Odds ratios (ORs) and 95% confidence intervals (CIs) for TT versus CC genotype, CT versus CC genotype, TT versus CT and CC genotype combined, and for T versus C allele.Result(s)Twenty-six studies with 2120 URPL cases and 2949 controls were included. Overall random-effects ORs of 1.49 (95% CI, 1.12–2.00) for TT versus CC genotype, 1.40 (95% CI, 1.11–1.77) for TT versus CT and CC genotype combined, and 1.21 (95%CI, 1.04-1.40) for T versus C allele were found. Stratified analysis showed that significant strong associations between MTHFR C677T polymorphism and URPL were present only in the five Chinese studies (OR = 2.96 for TT versus CC genotype; OR = 2.30 for TT versus CT+CC genotype; OR = 1.73 for T versus C allele), but not in any other studies, including the studies conducted in the European countries.Conclusion(s)The MTHFR C677T mutation is not a genetic risk factor for URPL except in a Chinese population.