The relation between erythrocyte volume and folate levels is influenced bya common mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (C677T)

Background: The enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) pla ys an important role in folate metabolism and folate-dependent reactions. H omozygosity for a common polymorphism in the MTHFR gene (C677T, Ala to Val) is associated with an increased risk of neural tube defects and hyperhomoc ysteinemia in individuals with low folate levels. Homozygous carriers of th e polymorphism with adequate folate levels, on the other hand, seem to be a t lower risk for colorectal cancer, Homozygous carriers of the polymorphism (5-15% of the white population) probably represent a subpopulation with in creased 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 par ameters. 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 s troke) and in 82 healthy subjects, Results: Homozygous carriers (VV) of the polymorphism with low folate level s showed significantly higher homocysteine levels than mutation-negative (A A) and heterozygous (AV) subjects (P=0.038), Furthermore, VV subjects in th e lowest folate quartile exhibited significantly higher mean erythrocyte vo lumes (MCV) and a tendency towards higher erythrocyte hemoglobin content (M CH) 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). Conclusion: We demonstrate an association between the C677T polymorphism, f olate levels, and hematological parameters. The elevation of MCV in homozyg ous carriers of the polymorphism with low folate levels indicates impaired DNA synthesis and/or methylation In these subjects, Considering our data an d the results of previous studies, the polymorphism may have contrary effec ts on homocysteine metabolism and DNA synthesis/methylation dependent on a subject's folate supply. Although the polymorphism is disadvantageous in ho mozygous carriers with low folate levels, its presence may be beneficial in individuals with adequate folate supply.