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Nutrient-Gene Interactions

Methylenetetrahydrofolate Reductase 677CT Variant Modulates Folate Status Response to Controlled Folate Intakes in Young Women

Cheryl L. Guinotte, Michael G. Burns, Juan A. Axume^*, Hiroko Hata, Tania F. Urrutia^*, Aaron Alamilla^*, Dale McCabe^*, Anny Singgih^*, Edward A. Cogger and Marie A. Caudill³

Human Nutrition and Food Science Department, ^* Biological Sciences Department and Animal and Veterinary Science Department, Cal Poly Pomona University, Pomona, CA 91768

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

A common genetic variant in the methylenetetrahydrofolate reductase (MTHFR) gene involving a cytosine to thymidine (CT) transition at nucleotide 677 is associated with reduced enzyme activity, altered folate status and potentially higher folate requirements. The objectives of this study were to investigate the effect of the MTHFR 677 T allele on folate status variables in Mexican women (n = 43; 18–45 y) and to assess the adequacy of the 1998 folate U.S. Recommended Dietary Allowance (RDA), 400 µg/d as dietary folate equivalents (DFE). Subjects (14 CC, 12 CT, 17 TT genotypes) consumed a low folate diet (135 µg/d DFE) for 7 wk followed by repletion with 400 µg/d DFE (7 CC, 6 CT, 9 TT) or 800 µg/d DFE (7 CC, 6 CT, 8 TT) for 7 wk. Throughout repletion with 400 µg/d DFE, the TT genotype had lower (P 0.05) serum folate and higher (P 0.05) plasma total homocysteine (tHcy) concentrations than the CC genotype. CT heterozygotes did not differ (P > 0.05) in their response relative to the CC genotype. Throughout repletion with 800 µg/d DFE, the CT genotype had lower (P 0.05) serum folate concentrations and excreted less (P 0.05) urinary folate than the CC genotype. However, there were no differences (P > 0.05) in the measured variables between the TT and CC genotypes. Repletion with 400 µg/d DFE led to normal blood folate and desirable plasma tHcy concentrations, regardless of MTHFR C677T genotype. Collectively, these data demonstrate that the MTHFR CT variant modulates folate status response to controlled folate intakes and support the adequacy of the 1998 folate U.S. RDA for all three MTHFR C677T genotypes.

KEY WORDS: • folate • homocysteine • human • MTHFR genotype • RDA

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