title: MTHFR 677C->T genotype is associated with folate and homocysteine concentrations in a large, population-based, double-blind trial of folic acid supplementation.
abstract: BACKGROUND
  The methylenetetrahydrofolate reductase (MTHFR) genotype is associated with modification of disease and risk of neural tube defects. Plasma and red blood cell (RBC) folate and plasma homocysteine concentrations change in response to daily intakes of folic acid supplements, but no large-scale or population-based randomized trials have examined whether the MTHFR genotype modifies the observed response.
  
  
  OBJECTIVE
  We sought to determine whether the MTHFR 677C→T genotype modifies the response to folic acid supplementation during and 3 mo after discontinuation of supplementation.
  
  
  METHODS
  Northern Chinese women of childbearing age were enrolled in a 6-mo supplementation trial of different folic acid doses: 100, 400, and 4000 μg/d and 4000 μg/wk. Plasma and RBC folate and plasma homocysteine concentrations were measured at baseline; after 1, 3, and 6 mo of supplementation; and 3 mo after discontinuation of supplementation. MTHFR genotyping was performed to identify a C→T mutation at position 677 (n = 932).
  
  
  RESULTS
  Plasma and RBC folate and homocysteine concentrations were associated with MTHFR genotype throughout the supplementation trial, regardless of folic acid dose. MTHFR TT was associated with lower folate concentrations, and the trend of TT < CC was maintained at even the highest doses. Folic acid doses of 100 μg/d or 4000 μg/wk did not reduce high homocysteine concentrations in those with the MTHFR TT genotype.
  
  
  CONCLUSIONS
  MTHFR genotype was an independent predictor of plasma and RBC folate and plasma homocysteine concentrations and did not have a significant interaction with folic acid dose during supplementation. This trial was registered at clinicaltrials.gov as NCT00207558.
authors.affiliation: National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors.forename: Krista S
authors.initials: KS
authors.lastname: Crider
authors.forename: Jiang-Hui
authors.initials: JH
authors.lastname: Zhu
authors.forename: Ling
authors.initials: L
authors.lastname: Hao
authors.forename: Quan-He
authors.initials: QH
authors.lastname: Yang
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Yang
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gindler
authors.forename: David R
authors.initials: DR
authors.lastname: Maneval
authors.forename: Eoin P
authors.initials: EP
authors.lastname: Quinlivan
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.forename: Lynn B
authors.initials: LB
authors.lastname: Bailey
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Berry
mesh_terms: D002681:China; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000097:blood* / Q000494:pharmacology; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012044:Regression Analysis
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)