The MTHFR gene encodes the vitamin-dependent enzyme, methylenetetrahydrofolate reductase. Several conditions or defects caused by functionally impaired forms of the MTHFR protein can be improved through dietary supplementation by folate.
There are 3 common SNPs giving rise to MTHFR alleles:
It is likely that there are numerous other variations that are much rarer. When the MTHFR genes of 564 individuals of diverse ethnicities were fully sequenced, in addition to the 3 common alleles mentioned above, 11 other nonsynonymous changes were found, each with a frequency under 1%. Four of these 11 rarer alleles affected enzyme function (as did A222V) based on tests in yeast, most of which could be fixed with higher folate supplementation (in yeast; this is not yet tested in humans). Since all five impaired alleles map to the N-terminal catalytic domain of the enzyme, it seems likely that additional SNPs causing nonsynonymous changes in this region could have similar effects.10.1073/pnas.0802813105
SNP rs1801133, A222V, is not thought to be a major risk factor for neural tube defects [PMID 17035141] except in certain populations. For example, Dutch and Irish populations indicate an increased risk for (T;T) carriers [PMID 10090889], but this same genotype (ie carriers of the thermolabile T allele) appears to have a protective effect in an Italian population studied [PMID 12111380].
[PMID 16672082] a SNP in MTHFR which affects Neural-tube defects (Birth defects)