Vitamin B12 Deficiency

Vitamin B12 processing also is linked to folate processing and hence genes that are associated with folate uptake and transport potentially may play a role in levels of functional B12 in the body. Further, reduction in elevated homocysteine can potentially be affected by the activity of cystathionine beta synthase.

Folate cycling enzymes

DHFR - Dihydrofolate reductase. This NADPH dependent enzyme reduces dihydrofolate to tetrahydrofolate, and is involved in processing of supplemental folic acid (folate) and in cycling folate within the folate cycle. Common SNPs rs1643649, rs1643659, rs1677693 and rs1650697, all appear to show similar frequencies, suggesting close genetic linkage.

FolR1, FolR2, FolR3 - Folate receptor. FolR1 and FolR2 are membrane bound receptors that are involved in unidirectional folate uptake into cells, whereas FolR3 is a soluble folate receptor. rs2071010 (FolR1) AA appears to be a conditionally lethal variant, so too rs7925545GG (FolR3). rs651933AA (FolR2) has been associated with an increased incidence of spina bifida, particularly Meningomyelocele (O'Bryne et al, 2010), and is more common in children with autism (personal observations.

MTHFD1L- Methylenetetrahydrofolate dehydrogenase. MTHFD1L is involved in the conversion of 5,10-methyelen-THF to 10-formyl-THF, which is a precursor of purine synthesis. There are at least 7 common variants of the gene, with some of the rarer variants being associated with Late Onset Alzheimer's Disease, such s rs11754661AA, rs1734974CC and rs803422AA (Ma et al 2012)

References

O'Byrne et al Association of folate receptor (FolR1, FolR2, FolR3) and reduced folate carrier (SLC19A1) genes with Meningomyelocele. PMC 3046546

Ma et al Replication of the MTHFRD1L gene association with late-onset Alzheimer's disease in a Northern Han Chinese population. PMD 22330827