title: Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations.
abstract: 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.
  
  
  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.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, Mass, USA.
authors.forename: P F
authors.initials: PF
authors.lastname: Jacques
authors.forename: A G
authors.initials: AG
authors.lastname: Bostom
authors.forename: R R
authors.initials: RR
authors.lastname: Williams
authors.forename: R C
authors.initials: RC
authors.lastname: Ellison
authors.forename: J H
authors.initials: JH
authors.lastname: Eckfeldt
authors.forename: I H
authors.initials: IH
authors.lastname: Rosenberg
authors.forename: J
authors.initials: J
authors.lastname: Selhub
authors.forename: R
authors.initials: R
authors.lastname: Rozen
mesh_terms: D000328:Adult; D000368:Aged; D005492:Folic Acid / Q000097:blood* / Q000627:therapeutic use; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood* / Q000235:genetics; D011110:Polymorphism, Genetic
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)