A variant form of methylenetetrahydrofolate reductase (MTHFR) (677C-->T) is a known risk factor for NTDs, but the prevalence of the risk genotype explains only a small portion of the protective effect of folic acid.
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 identified a common deletion/insertion polymorphism, rs3832406, c.781-6823ATT(7-9), which influences splicing efficiency and is strongly associated with NTD risk.
These results reveal that the association of SNP rs7646 and NTD risk involves differences in microRNA regulation and, highlights the importance of genotype-dependent differential microRNA regulation in relation to human disease risk.