Genetic polymorphisms and folate status

Abstract

Moderate hyperhomocysteinemia‐induced low folate status is an independent risk factor for cardiovascular disease, dementia, and depression. Folate is an essential cofactor in the one‐carbon metabolism pathway and is necessary in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation. In the folate cycle and homocysteine metabolism, folate, vitamin B12, vitamin B6, and vitamin B2 are important cofactors. Many enzymes are involved in folate transport and uptake, the folate pathway, and homocysteine (Hcy) metabolism, and various polymorphisms have been documented in these enzymes. Serum folate and total Hcy (tHcy) levels are influenced by folate intake and genetic polymorphisms in 5,10‐methylenetertahydrofolate reductase (MTHFR) such as C677T. The prevalence of the MTHFR 677TT genotype varies across ethnic groups and regions, with a frequency of approximately 15% in Japanese populations. Individuals with the TT genotype have significantly higher tHcy levels and lower folate levels in serum than those with the CT and TT genotypes. However, administration of folic acid has been shown to eliminate these differences. Moreover, data have suggested that interventions based on genotype may be effective for motivating individuals to change their lifestyle and improve their nutrition status. Accordingly, in this review, we discuss the effects of MTHFR C677T polymorphisms on serum tHcy and folate levels with folic acid intervention and evaluate approaches for overcoming folic acid deficiency and related symptoms.

The implication of single‐nucleotide polymorphisms in ovarian hyperstimulation syndrome

“…The MTHFR catalyzes the irreversible conversion of 5,10‐methylenetetrahydrofolate to 5‐methylenetetrahydrofolate, serving as a methyl donor in the remethylation of homocysteine to methionine (Ueland, Hustad, Schneede, Refsum, & Vollset, ). The SNPs in MTHFR are suggested to alter the levels of circulating folate and homocysteine (Hiraoka & Kagawa, ) and are associated with fetal malformations and spontaneous recurrent pregnancy loss (Zetterberg et al, ). Our data indicate that both rs1801131 and rs1801133 polymorphisms raise the risk of OHSS development.…”

Preconception folic acid supplementation use and the occurrence of neural tube defects in Japan: A nationwide birth cohort study of the Japan Environment and Children's Study

“…No genetic analysis was performed. 22 We were also not able to evaluate the effect of folic acid supplementation on the prevalence of NTDs quantitatively (μg) because of the absence of the data on the daily amount of supplementary folic acid intakes (μg) in the survey.…”

Food Intervention with Folate Reduces TNF-α and Interleukin Levels in Overweight and Obese Women with the MTHFR C677T Polymorphism: A Randomized Trial

“…Furthermore, high Hcy oxidation and body fat accumulation could lead to cytokine-mediated inflammation, and an increase in the oxidative stress. In addition, a balanced diet rich in antioxidants and anti-inflammatory nutrients like folate might be necessary to reduce this damage and also to avoid the C677T polymorphism effects [3,[13][14][15][16][17][18].…”