Relationship between unexplained recurrent pregnancy loss and 5,10-methylenetetrahydrofolate reductase) polymorphisms

Objective To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of folate metabolism-related genes. Design A case-control study. Setting Urban university-based hospital. Patient(s) Two-hundred and eighteen women with URPL and 264 healthy controls. Intervention(s) None. Main Outcome Measure(s) Fluorescence quantitative polymerase chain reaction examination of sequences of the C677T and A1298C loci of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Result(s) The frequency of the T allele at the MTHFR C677T locus in the URPL group was statistically significantly higher compared with the control group (odds ratio [OR] 1.324; 95% confidence interval [CI], 1.014–1.729), and the presence of the CC+CT genotype was statistically significantly reduced in the URPL group (OR 0.678; 95% CI, 0.471–0.974). The frequency of the C allele at the MTHFR A1298C locus in the URPL group was statistically significantly higher than that in the control group (OR 1.557; 95% CI, 1.066–2.275), and the presence of the CC+AC genotype was statistically significantly elevated in the URPL group (OR 1.740; 95% CI, 1.137–2.661). The frequency of MTHFR 677CT/1298AC compound genotypes in the URPL group was 6.589-fold higher compared with the control group. Most patients in the URPL group carried two mutant genes (69.3%), and the percentage of patients with two mutant genes was statistically significantly higher than in the control group (OR 4.996; 95% CI, 1.650–15.129). Conclusion(s) The MTHFR 1298AC genotype and composite heterozygote genotype (677CT/1298AC) are risk factors for URPL. The risk of URPL is highest in women carrying two mutations of A1298C and C677T locus in MTHFR.