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.
BACKGROUND:Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate, the major carbondonor 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.
Authors: J Richard Pilsner; Howard Hu; Robert O Wright; Katarzyna Kordas; Adrienne S Ettinger; Brisa N Sánchez; David Cantonwine; Alicia L Lazarus; Alejandra Cantoral; Lourdes Schnaas; Martha Maria Téllez-Rojo; Mauricio Hernández-Avila Journal: Am J Clin Nutr Date: 2010-05-26 Impact factor: 7.045
Authors: Susan M Wernimont; Andrew G Clark; Patrick J Stover; Martin T Wells; Augusto A Litonjua; Scott T Weiss; J Michael Gaziano; Pantel S Vokonas; Katherine L Tucker; Patricia A Cassano Journal: J Nutr Date: 2012-05-30 Impact factor: 4.798