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D.et al (2014)

Data availability Nucleotide sequences of codon-optimized genes can be found in Supplementary Table 6

MTHFR (Methylene Tetrahydrofolate Reductase) An important enzyme that helps biotransform 5,10 methylene tetrahydrofolate into methylated folate Some people have a variant of the normal gene known as the MTHFR gene (a single nucleotide polymorphism) which impairs proper methylation An MTHFR SNP can contribute to high homocysteine and related diseases MTHFR Variants (or single nucleotide polymorphisms =SNP) There are two relatively common SNPs: A1298C clinically irrelevant will not effect homocysteine levels does not require any specific supplementation C677T can effect homocysteine levels patient may need more folate or 5-methyl-folate Utilizing the methionine pathway by adding methyl donors like trimethyglycine and choline can bypass the problem of MTHFR variants Manifestations of Elevated Homocysteine Sources of Methyl Groups B vitamins folate, B-6, B-12 Trimethylglycine (betaine) Choline Methionine SAMe Metabolically Directed Approach to Elevated Homocysteine Look for root causes of homocysteine elevation chronic inflammation, hypothyroidism, poor diet, MTHFR variants When replacing needed B vitamins, take into account the patients individual metabolic needs For example, a Dysaerobic patient will benefit from folate, but may suffer from increased Dysaerobic imbalance from B-6 and B-12

Lo, M., Wang, Y.-Z

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