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Nutrient-Gene Interactions

The Methylenetetrahydrofolate Reductase 677CT Polymorphism and Dietary Folate Restriction Affect Plasma One-Carbon Metabolites and Red Blood Cell Folate Concentrations and Distribution in Women^1,2

Steven R. Davis, Eoin P. Quinlivan, Karla P. Shelnutt, David R. Maneval, Haifa Ghandour, Antonieta Capdevila, Bonnie S. Coats^*, Conrad Wagner, Jacob Selhub, Lynn B. Bailey, Jonathan J. Shuster^**, Peter W. Stacpoole^*, and Jesse F. Gregory, III³

Food Science & Human Nutrition Department, Institute of Food and Agricultural Sciences, ^* Division of Endocrinology and Metabolism, Department of Medicine, Department of Biochemistry and Molecular Biology, and ^** Department of Statistics, College of Medicine, University of Florida, Gainesville, FL 32611-0370; Vitamin Metabolism, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111; Department of Biochemistry, Vanderbilt University, and Department of Veterans Affairs Medical Center, Nashville, TN 37232

³To whom correspondence should be addressed. E-mail: jfgy{at}ufl.edu.

Whether folate status and the methylenetetrahydrofolate reductase (MTHFR) 677CT 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 677CT 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 µg 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.

KEY WORDS: • homocysteine • methionine • S-adenosylmethionine • S-adenosylhomocysteine • women

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