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G80A reduced folate carrier SNP modulates cellular uptake of folate and affords protection against thrombosis via a non homocysteine related mechanism.

Abstract
Dietary folate is absorbed in the jejunum by the 'Reduced Folate Carrier' binding protein. This protein also sequesters extracellular folate for use by many cells in the body. As several biosynthetic pathways require folate for critical life processes, any change in the properties of this protein could lower folate bioavailability, cellular levels of the vitamin, and thus influence health. Since folate lowers thrombogenic homocysteine, we examined the prevalence of a common genetic polymorphism encoding the Reduced Folate Carrier (G80A RFC) to see if it acts as a risk factor for thrombotic vascular disease via an effect on homocysteine disposition in a cohort of 156 patients. The odds ratio indicates a significant protective effect of the mutant A allele against thrombosis: OR = 0.56(95% CI; 0.34-0.92). chi2; p = 0.022 (Yates corrected chi2; p = 0.031). The polymorphism had no impact on homocysteine, but did increase the level of extracellular to intracellular folate as might be predicted by the biological role of the expressed protein. This, and not homocysteine level, may be what affords protection against thrombosis.
AuthorsZoe Yates, Mark Lucock
JournalLife sciences (Life Sci) Vol. 77 Issue 22 Pg. 2735-42 (Oct 14 2005) ISSN: 0024-3205 [Print] Netherlands
PMID15964598 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Membrane Transport Proteins
  • Reduced Folate Carrier Protein
  • SLC19A1 protein, human
  • Homocysteine
  • Folic Acid
Topics
  • Aged
  • Analysis of Variance
  • Chromatography, High Pressure Liquid
  • Female
  • Fluorescence
  • Folic Acid (blood, pharmacokinetics)
  • Homocysteine (metabolism)
  • Humans
  • Jejunum (metabolism)
  • Male
  • Membrane Transport Proteins (genetics, metabolism)
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Reduced Folate Carrier Protein
  • Risk Factors
  • Thrombosis (genetics, metabolism)

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