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

J Nutr Sci Vitaminol (Tokyo). 2014;60(4):231-8. doi: 10.3177/jnsv.60.231.


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 (β=0.165, p=0.066) or CT (β=0.248, p<0.001) genotypes, and with lower tHcy levels only among those with the CC (β=-0.141, p=0.013) genotype. Plasma folate was significantly and inversely associated with tHcy, irrespective of MTHFR genotype. When the analysis was restricted to those with tHcy levels higher than the reference range (≥13.5 nmol/mL, n=20), these significant associations were not found. The interaction between folate intake or plasma folate and genotype was not significant in any analysis. In conclusion, dietary folate intake was positively associated with plasma folate among those with the CC or CT genotypes and inversely associated with tHcy among those with the CC genotype, but the associations were not clear among those with higher levels of tHcy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Asians
  • Cross-Sectional Studies
  • Diet*
  • Female
  • Folic Acid / administration & dosage
  • Folic Acid / blood
  • Folic Acid / genetics*
  • Genotype*
  • Homocysteine / blood
  • Homocysteine / genetics*
  • Humans
  • Japan
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Nutritional Status / genetics*
  • Polymorphism, Genetic*


  • Homocysteine
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)