title: The glycine N-methyltransferase (GNMT) 1289 C->T variant influences plasma total homocysteine concentrations in young women after restricting folate intake.
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 microg/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 < or = 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.
authors.affiliation: Human Nutrition and Food Science Department, Cal Poly Pomona University, CA 91768, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Beagle
authors.forename: Tai Li
authors.initials: TL
authors.lastname: Yang
authors.forename: Jean
authors.initials: J
authors.lastname: Hung
authors.forename: Edward A
authors.initials: EA
authors.lastname: Cogger
authors.forename: David J
authors.initials: DJ
authors.lastname: Moriarty
authors.forename: Marie A
authors.initials: MA
authors.lastname: Caudill
mesh_terms: D000328:Adult; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000201:enzymology*; D050938:Glycine N-Methyltransferase / Q000235:genetics*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C494510:GNMT protein, human; D050938:Glycine N-Methyltransferase