Folate Insufficiency Due to MTHFR Deficiency Is Bypassed by 5-Methyltetrahydrofolate

摘要: Adequate levels of folates are essential for homeostasis the organism, prevention congenital malformations, and salvage predisposed disease states. They depend on genetic predisposition, therefore, a pharmacogenetic approach to individualized supplementation or therapeutic intervention is necessary an optimal outcome. The role in vital cell processes was investigated by translational pharmacogenetics employing lymphoblastoid lines (LCLs). Depriving cells led reversible S-phase arrest. Since 5,10-methylenetetrahydrofolate reductase (MTHFR) key enzyme biosynthesis active folate form, we evaluated relevance polymorphisms MTHFR gene intracellular bioactive metabolite, 5-methyltetrahydrofolate (5-Me-THF). LCLs (n = 35) were divided into low- normal-MTHFR activity groups based their genotype. cultured presence folic acid (FA) 5-Me-THF. Based cells' metabolic 5-Me-THF levels, conclude FA sufficient maintain adequate level normal group, while low require overcome defects caused genes. This finding supported determination lysates LC-MS/MS. resulted 2.5-fold increase with activity, but there no after cells. However, when exposed 5-Me-THF, 10-fold this metabolite determined. These findings indicate that patients undergoing counteract anti-folate therapies, increased demand, would benefit from pharmacogenetics-based therapy choices.