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© 2005 American Society for Nutrition J. Nutr. 135:2780-2785, December 2005


Nutrient-Gene Interactions

The Glycine N-Methyltransferase (GNMT) 1289 C->T Variant Influences Plasma Total Homocysteine Concentrations in Young Women after Restricting Folate Intake1

Brandon Beagle, Tai Li Yang, Jean Hung, Edward A. Cogger*, David J. Moriarty{dagger} and Marie A. Caudill2

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

2To whom correspondence should be addressed. E-mail: macaudill{at}csupomona.edu.

ABSTRACT

Glycine N-methyltransferase (GNMT) is a key regulatory protein in folate metabolism, methionine availability, and transmethylation reactions. Perturbations in GNMT may lead to aberrations in homocysteine metabolism, a marker of numerous pathologies. The primary objective of this study was to examine the influence of the GNMT 1289 C->T alone, and in combination with the methylenetetrahydrofolate reductase (MTHFR) 677 C->T variant, on plasma total homocysteine concentrations in healthy young women (n = 114). Plasma total homocysteine was measured at baseline (wk 0) and after 2 wk of controlled folate restriction (135 µg/d as dietary folate equivalents). Plasma homocysteine concentrations did not differ among the GNMT C1289T genotypes at baseline. However, after folate restriction, women with the GNMT 1289 TT genotype (n = 16) had higher (P = 0.019) homocysteine concentrations than women with the CT (n = 51) or CC (n = 47) genotype. The influence of the GNMT 1289 C->T variant on homocysteine was dependent on the MTHFR C677T genotype. In subjects with the MTHFR 677 CC genotype, homocysteine was greater (P ≤ 0.05) for GNMT 1289 TT subjects relative to 1289 CT or CC subjects. However, in subjects with the MTHFR 677 TT genotype, plasma homocysteine concentrations did not differ among the GNMT C1289T genotypes. Overall, these data suggest that the GNMT 1289 C->T polymorphism influences plasma homocysteine and is responsive to folate intake.


KEY WORDS: • glycine N-methyltransferase • methylenetetrahydrofolate reductase • methionine synthase reductase • homocysteine • folate • women




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