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American Journal of Clinical Nutrition, Vol. 77, No. 3, 687-693, March 2003
© 2003 American Society for Clinical Nutrition


Original Research Communication

Effect of the methylenetetrahydrofolate reductase 677C->T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample1,2,3

Angelika de Bree, WM Monique Verschuren, Anne-Lise Bjørke-Monsen, Nathalie MJ van der Put, Sandra G Heil, Frans JM Trijbels and Henk J Blom

1 From the Department of Chronic Disease Epidemiology, National Institute of Public Health and the Environment, Bilthoven, Netherlands (AdB and WMMV); the Laboratory of Pediatrics and Neurology, University Medical Center Nijmegen, Nijmegen, Netherlands (AdB, NMJvdP, SGH, FJMT, and HJB); the Scientific and Technical Institute of Nutrition and Food, U557 INSERM/U1125 INRA/ISTNA-CNAM, Paris (AdB); and the LOCUS for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway (A-LB-M).

Background: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate and homocysteine metabolism. The common MTHFR 677C->T polymorphism decreases the enzyme’s activity.

Objective: The objective of the study was to assess the effect of the polymorphism on the relations among folate intake, plasma folate concentration, and total plasma homocysteine (tHcy) concentration.

Design: The design was a cross-sectional analysis in a random sample (n = 2051) of a Dutch cohort (aged 20–65 y).

Results: At a low folate intake (166 µg/d), folate concentrations differed significantly among the genotypes (7.1, 6.2, and 5.4 nmol/L for the CC, CT, and TT genotypes, respectively; P for all comparisons < 0.05). At a high folate intake (250 µg/d), folate concentrations in CT and CC subjects did not differ significantly (8.3 and 8.6 nmol/L, respectively, but were significantly higher (P = 0.2) than those in TT subjects (7.3 nmol/L; P = 0.04). At a low folate concentration (4.6 nmol/L), TT subjects had a significantly higher (P = 0.0001) tHcy concentration than did CC and CT subjects (20.3 compared with 15.0 and 14.1 µmol/L, respectively), whereas at a high folate concentration (11.9 nmol/L), the tHcy concentration did not differ significantly between genotypes (P > 0.2; <13.1 for all genotypes). The relation between folate intake and tHcy concentration had a pattern similar to that of the relation between plasma folate and tHcy concentrations.

Conclusions: At any folate intake level, TT subjects have lower plasma folate concentrations than do CT and CC subjects. Yet, at high plasma folate concentrations, tHcy concentrations in TT subjects are as low as those in CT and CC subjects.

Key Words: Methylenetetrahydrofolate reductase • MTHFR • folate intake • plasma folate concentration • plasma homocysteine concentration • total homocysteine • tHcy • metabolism • Dutch population




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