rs1801394(G;G)

This common variant (HapMap allele frequency of 31.3%) in a protein involved in folate (B9) and cobalamin (B12) metabolism and is often reported as "MTRR I22M" (for the Ile to Met substitution at amino acid 22). Mothers homozygous for this variant were found in a few studies to have an increased risk for Down syndrome babies (risk of 0.4%, average risk in population is 0.25%), but other studies (including in Italian, Irish, French, and Indian-Gujarati women) found no increased risk. Notably, age plays a far larger role in the rate of Down syndrome (risk is 4.5% for a mother 45-years-of-age), and, it is unknown how this variant may combine with the effect of age. There are conflicting reports associating this variant with incidence of neural tube defects, possibly when combined with MTHFR A222V.