The presence of the MTHFR C677T polymorphism was studied by Kaur (2013) in 110 mothers of children with Down’s Syndrome against 111 controls in India. Results from this present study had the 677TT genotype to be present in 1.8% of the case group, whilst none of the control group carried. The frequency of a T allele in cases was 0.13, compared with 0.11 in controls. Therefore, neither of these findings were stated as significant between cases and controls. The author stated no association between the C677T mutation and the risk of non-disjunction (the separation of chromosomes during meiosis).
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.