For MTHFD1rs2236225 polymorphism, mothers having GA genotype and A allele exhibited an increased risk of NTDs in the offspring (OR = 2.600, 95%CI: 1.227-5.529; OR = 1.847, 95%CI: 1.047-3.259).
For rs2236225 within MTHFD1, children with allele A or genotype AA had a high NTDs risk (OR=1.500, 95%CI=1.061~2.120; OR=2.862, 95%CI=1.022~8.015, respectively).
Our research provides the first evidence supporting a paternal, rather than a maternal, transmission bias of MTHFD1G1958A variant for NTD susceptibility in the offspring.
In our study, an increased risk of NTD was observed for 1958G>A of MTHFD1 (AA vs. GG: OR=2.63, 95% CI=2.61-5.70; AA vs. GG+GA: OR=2.10, 95% CI=1.07-4.14; A vs. G: OR=1.62, 95% CI=1.11-2.36).
Gene variants in the folate metabolic pathway (e.g., MTHFR rs1801133 (677 C > T) and MTHFD1rs2236225 (rs2236225" genes_norm="1788;4522">R653Q)) have been found to increase NTD risk.
Having previously identified a polymorphism within the cytoplasmic folate enzyme, MTHFD1, as a maternal risk factor for NTDs, we considered the more recently identified mitochondrial paralogue, MTHFD1L, as a candidate gene for NTD association.
In summary, our results indicate that heterozygosity and homozygosity for the MTHFD1 1958G > A polymorphism are genetic determinants of NTD risk in the cases examined.
We have established that the MTHFD1 1958G>A polymorphism has a significant role in influencing a mother's risk of having an NTD-affected pregnancy in the Irish population.
In summary, our results indicate that heterozygosity and homozygosity for the MTHFD1 1958G > A polymorphism are genetic determinants of NTD risk in the cases examined.
We have established that the MTHFD1 1958G>A polymorphism has a significant role in influencing a mother's risk of having an NTD-affected pregnancy in the Irish population.
We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival.
We conclude that genetic variation in the MTHFD1 gene is associated with an increase in the genetically determined risk that a woman will bear a child with NTD and that the gene may be associated with decreased embryo survival.