title: The relation between erythrocyte volume and folate levels is influenced by a common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T).
abstract: BACKGROUND
  The enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) plays an important role in folate metabolism and folate-dependent reactions. Homozygosity for a common polymorphism in the MTHFR gene (C677T, Ala to Val) is associated with an increased risk of neural tube defects and hyperhomocysteinemia in individuals with low folate levels. Homozygous carriers of the polymorphism with adequate folate levels, on the other hand, seem to be at lower risk for colorectal cancer. Homozygous carriers of the polymorphism (5-15% of the white population) probably represent a subpopulation with increased folate needs. Hematological sequelae of folate deficiency have been recognized for a long time. However, no data exist concerning the relation between the C677T MTHFR polymorphism, folate levels, and hematological parameters.
  
  
  METHODS
  We investigated associations between the C677T MTHFR polymorphism, folate levels, total plasma homocysteine, and hematological parameters in 94 patients with cerebrovascular disease (transient ischemic attack/minor stroke) and in 82 healthy subjects.
  
  
  RESULTS
  Homozygous carriers (VV) of the polymorphism with low folate levels showed significantly higher homocysteine levels than mutation-negative (AA) and heterozygous (AV) subjects (P = 0.038). Furthermore, VV subjects in the lowest folate quartile exhibited significantly higher mean erythrocyte volumes (MCV) and a tendency towards higher erythrocyte hemoglobin content (MCH) than AA and AV subjects (P = 0.008 and 0.069, respectively). Although MCV was not influenced by folate levels in AA and AV subjects, in VV subjects a significant inverse correlation with folate levels could be demonstrated (P = 0.544 and 0.020, respectively).
  
  
  CONCLUSIONS
  We demonstrate an association between the C677T polymorphism, folate levels, and hematological parameters. The elevation of MCV in homozygous carriers of the polymorphism with low folate levels indicates impaired DNA synthesis and/or methylation in these subjects. Considering our data and the results of previous studies, the polymorphism may have contrary effects on homocysteine metabolism and DNA synthesis/methylation dependent on a subject's folate supply. Although the polymorphism is disadvantageous in homozygous carriers with low folate levels, its presence may be beneficial in individuals with adequate folate supply.
authors.affiliation: University Clinic for Neurology, Vienna, Austria. wolfgang.lalouschek@univie.ac.at
authors.forename: W
authors.initials: W
authors.lastname: Lalouschek
authors.forename: S
authors.initials: S
authors.lastname: Aull
authors.forename: W
authors.initials: W
authors.lastname: Serles
authors.forename: M
authors.initials: M
authors.lastname: Wolfsberger
authors.forename: L
authors.initials: L
authors.lastname: Deecke
authors.forename: I
authors.initials: I
authors.lastname: Pabinger-Fasching
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000097:blood / Q000201:enzymology / Q000235:genetics; D004911:Erythrocyte Volume / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)