The presence of the MTHFR C677T mutation was studied in a group of mothers with Down’s Syndrome children. Results found the 677TT genotype to be present in 1.8% of the case group, with none of the women in the control group found to be carrying this genotype. The frequency of a T allele in cases was 0.13, compared with 0.11 in controls. Therefore, neither of these findings were found to be positively linked with the increased risk of developing Down’s Syndrome in offspring.
In addition to this study containing a small sample size, the researchers state that this study may not have yielded a positive link between MTHFR mutations and DS prevalence as the C677T mutation was studied alone, with the possibility of the A1298C mutation playing an unknown role in this population.
Furthermore, as this study was based on an Indian population, the high prevalence of vegetarians found in this ethnicity may also play a causative role in the development of DS in offspring.
A dietary deficiency in B12 will decrease methylation even in the absence of a MTHFR mutation, as the pathway does not have sufficient nutritional support to fully function. Therefore, the spread of MTHFR 677 genotypes may be evenly spread across this population sample, but may not provide clear evidence, as even those with a healthy C677C genotype may be undermethylating.
Overall, large amounts of evidence does support a relationship between MTHFR and DS, with individual population groups have differing environmental factors that are also affecting methylation and MTHFR mutation expression.