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.