title: The methylenetetrahydrofolate reductase 677C->T polymorphism and dietary folate restriction affect plasma one-carbon metabolites and red blood cell folate concentrations and distribution in women.
abstract: Whether folate status and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T polymorphism interact to affect methionine-cycle metabolite concentrations is uncertain. We evaluated the effects of dietary folate restriction on relations among folate status indices and plasma concentrations of methionine cycle metabolites in women with the MTHFR 677 C/C and T/T genotypes. Healthy, normohomocysteinemic women (n = 18; 20-30 y old) of adequate B vitamin status, and equally divided according to MTHFR 677C-->T genotype (9 C/C and 9 T/T) were recruited. Folate status indices and methionine cycle metabolites were measured in blood samples collected at baseline and after 7 wk of dietary folate restriction (115 microg dietary folate equivalents/d). Significant negative correlations between plasma total homocysteine concentrations and total or 5-methyl folate concentrations (P = 0.041 and 0.023, respectively) in RBCs were found only in T/T subjects. Formylated folates were detected in RBCs of T/T subjects only, and their abundance was predictive of plasma total homocysteine concentration despite no significant alteration by folate restriction. Plasma concentrations of S-adenosylmethionine and S-adenosylhomocysteine were not significantly affected by dietary folate restriction and the MTHFR 677 T/T genotype. In conclusion, plasma total homocysteine concentrations in subjects with the MTHFR 677 T/T genotype were inversely related to 5-methyl folate concentrations and directly related to formylated folate concentrations in RBCs, even though the latter were not significantly affected by moderate folate restriction.
authors.affiliation: Food Science & Human Nutrition Department, Institute of Food and Agricultural Sciences, College of Medicine, University of Florida, Gainesville, FL 32611-0370, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Davis
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Quinlivan
authors.forename: Karla P
authors.initials: KP
authors.lastname: Shelnutt
authors.forename: David R
authors.initials: DR
authors.lastname: Maneval
authors.forename: Haifa
authors.initials: H
authors.lastname: Ghandour
authors.forename: Antonieta
authors.initials: A
authors.lastname: Capdevila
authors.forename: Bonnie S
authors.initials: BS
authors.lastname: Coats
authors.forename: Conrad
authors.initials: C
authors.lastname: Wagner
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Bailey
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stacpoole
authors.forename: Jesse F
authors.initials: JF
authors.lastname: Gregory
mesh_terms: D019943:Amino Acid Substitution; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005494:Folic Acid Deficiency / Q000097:blood*; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)