Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study

Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease

“…We, however, observed an association between decreased folate levels and the wild-type MTHFR 1298AA genotype. Low folate concentrations in carriers of the MTHFR 1298AA genotype were reported by Kapiszewska et al [49] According to these authors, 677TT homozygous individuals are frequently carriers of the 1298AA genotype; this condition can explain the reduction of the MTHFR enzyme activity and, consequently, the decreased formation of 5-methyltetrahydrofolate, which is the main form of circulating folate [50]. However, in our study, a reduction of folate concentrations in individuals with combined genotype 677TT/1298AA was not observed (data not shown).…”

Human mutations in methylenetetrahydrofolate dehydrogenase 1 impair nuclear de novo thymidylate biosynthesis

“…The enrichment of formate into de novo dTMP was impaired in patient fibroblasts by 50% (Table 1), with a 15% increase in uracil content in DNA, likely resulting from uracil misincorporation during DNA synthesis as occurs in folate deficiency (24,25). Formate incorporation into dTMP has been shown in isolated nuclei (12), and this study shows the importance of MTHFD1 and formate in nuclear dTMP and DNA synthesis.…”

The effects of methyl-donor deficiency on mutation induction and transgenerational instability in mice

“…Uracil misincorporation can also be affected by genetic factors such as folate-related single nucleotide polymorphisms (SNPs), like the MTHFR 667 C->T variant (Knock et al, 2006;Knock et al, 2008;De Vos et al, 2008). Additionally, folate fortification (Hazra et al, 2010) and vitamin B 12 levels (Fenech 1998;Kapiszewska et al, 2005) could play an important role to the level of uracil misincorporation in the cells (Christensen et al, 2011). Adapted from Ames & Wakimoto, 2002.…”