A Cross-Sectional Study to Find Out the Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Genotype with Plasma Levels of Folate and Total Homocysteine by Daily Folate Intake in Japanese

Abstract

l-5-Methyl-tetrahydrofolate (THF), derived from dietary folate, is involved in the conversion of homocysteine into methionine ( Fig. 1; 1-3). Folate deficiency increases total homocysteine (tHcy) levels (4). Hyperhomocysteinemia is one of the risk factors of cardiovascular disease (4,5) and neural tube defects (NTDs) (6). Maintaining adequate blood folate levels and controlling tHcy levels are important in preventing these diseases.In the folate metabolic pathway, 5,10-methylene-THF is converted into 5-methyl-THF by the enzyme 10-methylene-THF reductase (MTHFR). In the MTHFR C677T polymorphism (rs 1801133), the T allele reduces thermostability of the enzyme and lowers its activity, which were found to be decreased by 30% in heterozygotes and by 65% in homozygotes of minor alleles compared with the CC genotype in an in vitro study (7). However, folate intake could increase blood folate levels even among those with the TT genotype. In previous observational studies, decreased tHcy levels were related to increased blood folate levels (8-11), and increased folate intake was associated with increased blood folate levels (8, 12) and decreased tHcy levels (8,13,14) in each of the MTHFR genotype. These correlations were substantially stronger among those with TT (8,9,[11][12][13][14][15] and those consuming relatively lower amounts of folate (8,12,13). In previous interventional studies using folate supplements or fortified foods, increased folate intake raised blood folate (16-21) and reduced tHcy levels (17-21).However, one study in Japan found no association of serum folate with energy-adjusted folate intake among those with the TT genotype (22). This may be partly explained by the difference in the amount of folate intake and sources of folate. The mean folate intake among Japanese aged 20 y or more was 329 mg/d for men and 189 mg/d for women and the mean intake from supplements or fortified foods among the population was only 1 mg/d in 2008 (23 (Received November 12, 2013) Summary In those with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, enzyme activity is lowered. Therefore, these individuals might require an increased intake of folate to maintain or control blood levels of plasma folate or total homocysteine (tHcy). We examined associations of dietary folate intake with fasting plasma folate and total homocysteine (tHcy) according to genotype among 554 Japanese (207 men and 347 women aged 39-89 y) recruited in 2009. Intake of folate was estimated with a food frequency questionnaire. The MTHFR polymorphism was genotyped by a polymerase chain reaction with confronting two-pair primers. The log-transformed concentration of folate or tHcy was regressed on energy-adjusted folate intake in a linear regression analysis. Higher folate intake was associated with higher plasma folate among those with the CC (b50.165, p50.066) or CT (b50.248, p,0.001) genotypes, and with lower tHcy levels only among those with the CC (b520.141, p50.013) genotype. Plasma folate was significantly and inversely associat...

Mediterranean diet–gene interactions: A targeted metabolomics study in Greek‐Cypriot women

“…Carriers of the minor 677T MTHFR rs1801133 alleles (677CT and 677TT) have a decreased enzymatic activity, which would lead to a low 5-MTHF production, whereas 677CC homozygotes retain the normal enzymatic activity, producing 5-MTHF effectively [45,46]. When the 677CC genotype is further (10 of 14) 1600558 combined with a high intake of plant-based food groups and thus a high dietary folate intake, the 5-MTHF concentration could be further augmented, as shown in our results as well as in previous studies [47,48]. Indeed, a high folate status and an increased 5-MTHF concentration, not only in 677CC carriers but also in 677TT carriers, was shown to be associated with a decreased risk for cancer development, potentially related with an adequate global DNA methylation status [36,49].…”

What do we know about homocysteine and exercise? A review from the literature

“…and its synthetized enzyme plays a key role in folate metabolism, which is an integral process for DNA and RNA synthesis and in protein methylation. This enzymatic activity process is lowered in subjects with MTHFR 677TT genotype and these individuals might require an increased intake of folate to maintain or control blood levels of plasma folate or tHcy [8,9].…”

Women with Methylenetetrahydrofolate Reductase Gene Polymorphism and the Need for Proper Periconceptional Folate Supplementation

“…1) and includes THF (tetrahydrofolate), 5-10-methylene-THF (5, 10-methylenetetrahydrofolate), L-5-methyl-THF (L-5-methyltetrahydrofolate) and 10-formyl-THF (10-formyltetrahydrofolate). The 10-formyl-THF and 5-10-methylene-THF are used in the synthesis of purines and pyrimidines, respectively while the L-5-methyl-THF serves as a methyl donor in the conversion of homocysteine to methionine [7,8]. Folic acid is a synthetic form of folate and is the most oxidized form.…”

“…Cytosine which is normally found at position 677 is replaced with a thymine residue and this results in valine being substituted for alanine [12,18]. The homozygous polymorphism (C677TT) reduces enzymatic activity by 70%, while the heterozygous polymorphism (C677CT) results in approximately 35% reduction of enzymatic activity [7]. The A1298C polymorphism results from a single nucleotide change at exon 7 where adenosine is replaced by cytosine and as a result glutamate is substituted for alanine.…”