Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations

Circulation. 1996 Jan 1;93(1):7-9. doi: 10.1161/01.cir.93.1.7.


Background: Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate, the major carbon donor in remethylation of homocysteine to methionine. A common MTHFR mutation, an alanine-to-valine substitution, renders the enzyme thermolabile and may cause elevated plasma levels of the amino acid homocysteine.

Methods and results: To assess the potential interaction between this mutation and vitamin coenzymes in homocysteine metabolism, we screened 365 individuals from the NHLBI Family Heart Study. Among individuals with lower plasma folate concentrations ( < 15.4 nmol/L), those with the homozygous mutant genotype had total fasting homocysteine levels that were 24% greater (P<.05) than individuals with the normal genotype. A difference between genotypes was not seen among individuals with folate levels > or = 15.4 nmol/L.

Conclusions: Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocysteine concentrations; folate supplementation may be necessary to prevent fasting hyperhomocysteinemia in such persons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Folic Acid / blood*
  • Folic Acid / therapeutic use
  • Genotype
  • Homocysteine / blood*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Middle Aged
  • Mutation
  • Oxidoreductases Acting on CH-NH Group Donors / blood*
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Polymorphism, Genetic


  • Homocysteine
  • Folic Acid
  • Oxidoreductases Acting on CH-NH Group Donors
  • Methylenetetrahydrofolate Reductase (NADPH2)