Correlation of Polymorphism of MTHFRs and RFC-1 Genes with Neural Tube Defects in China

Background: Maternal periconceptional supplementation of folate reduces the incidence of neonatal Neural Tube Defects, indicating that changes in folate metabolism play a role in formation of NTDs. The mutations on two genes involved in folate metabolism, the C677 of the MTHFR gene and the RFC-1(A80G) gene are potential risk factors of NTDs.

Methods: In this study, we analyzed the genotypic distributions and allele frequencies of MTHFR C677T and RFC-1 A80G polymorphisms in DNA samples from mothers with at least one previous child with NTDs (the NTD group) and controls.

Results: Our results indicated that there was a significant difference in the genotype and allele frequencies of RFC-1 80A-->G between the NTD group and controls (p = .008 and p = .017, respectively). There was, however, no significant difference in the genotype and allele frequencies of the MTHFR 677C-->T polymorphism between the NTD group and controls. The NTD group was further separated into the upper and lower types by location of abnormalities. The frequency of RFC-1 80A/G and 80G/G was significantly higher in the upper group than the control (p = .009 and p = .005, respectively). The frequency of G-alleles was also significantly higher in the upper group than the control (OR 2.42; p = .006; 95% CI: 1.28-4.58). For the MTHFR C677 gene, the frequency of T-alleles was significantly lower in the lower defect type than the control group (OR 0.32; p = .027; 95% CI: 0.11-0.9).

Conclusions: These results suggest that in the Shanxi population RFC-1 polymorphisms may play a role in NTD risk, whereas the impact of MTHFR C677T polymorphisms requires further clarification. Birth Defects Research (Part A) 2008.