Genetic variations of MTHFR gene and their association with preterm birth in Korean women

Background and objective: The MTHFR gene encodes the methylenetetrahydrofolate reductase known to be involved in the homocysteine–methionine pathway. It has been reported that the deficiency of MTHFR activity may cause hyperhomocysteinemia which results in adverse pregnancy outcomes. Previous studies reported a correlation between the MTHFR gene polymorphisms (677 T/C and 1298 A/C) and lower MTHFR activity and its association with preterm birth in various populations. Since these results were conflicting, we analyzed the genetic association of MTHFR gene 677 T/C and 1298 A/C polymorphisms with preterm birth in Korean women. Materials and methods: The subjects for case–control study were collected a total of 226 Korean women (98 preterm-birth patients and 128 controls). Genotype frequency differences between the case and the control were assessed using chi-square tests. Mann–Whitney t-test was used to estimate the effects of 1298 A/C genotype on clinicopathological characteristics (systolic blood pressure, diastolic blood pressure, birth weight, and gestational age at delivery) in preterm-birth patients. Results: Our results showed that the MTHFR 677 C/T polymorphism was significantly associated with preterm-birth patients in the analysis of genotype frequency (P = 0.044) and the over-dominant model (OR = 0.54; 95% CI, 0.320–0.920; P = 0.023). The recessive model showed a marginal trend toward significance (OR = 0.47; 95% CI, 0.220–1.010; P = 0.046). The 1298 A/C polymorphism was also associated with reduced preterm-birth risk in the recessive model (P = 0.032). In the correlation analysis, the 1298 C allele was significantly associated with increasing of gestational age at delivery in preterm-birth patients (P = 0.034). Conclusions: Our findings suggested that the MTHFR gene 677 C/T and 1298 A/C polymorphisms might have protective effects for preterm birth in the Korean women.