Evaluating the Association Between Genetic Polymorphisms Related to Homocysteine Metabolism and Unexplained Recurrent Pregnancy Loss in Women

OBJECTIVE: To investigate the relationship between unexplained recurrent pregnancy loss (URPL) and polymorphisms of homocysteine metabolism-related genes in women. MATERIALS AND METHODS: A case–control study included 90 women with two or more consecutive unexplained pregnancy losses and 92 controlled women without miscarriage history; the female participants were in the age category of 18–35 years. The high-resolution melting technique was used to detect the single-nucleotide variants related to homocysteine metabolism disorder, namely MTHFR C677T, MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphism. RESULTS: The MTHFR C677T polymorphism had significantly correlation with URPL. Indeed, the frequency of the677T allele and genotypes (677CT, 677TT) in the URPL group was significantly higher than that in the control group (p < 0.05). However, the allele, as well as genotype distribution of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms showed no significant difference (p > 0.05). MTHFR 677CT-1298AC genotype combination led to a 9.0-fold increased risk of URPL (OR 9.0; 95% CI, 2.25–35.99; p = 0.001), while the risk increased 10.0-fold (OR 10.0; 95% CI, 1.8–55.53; p = 0.008) when participants had more than the 3 variant loci. CONCLUSION: The MTHFR C677T polymorphism was a risk factor for URPL, and determining the MTHFR C677T polymorphism had a potential prediction of URPL risk. Moreover, the MTHFR C677T and MTHFR A1298C joint mutants might have a synergistic effect on URPL. Conversely, there is a lack of evidence suggesting the URPL risk of MTHFR A1298C, MTR A2756G, and MTRR A66G polymorphisms.