title: A polymorphism (80G->A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia.
abstract: 5-methyltetrahydrofolate is the predominant form of folate in plasma. It may be the preferred substrate for transport via the reduced-folate carrier (RFC). We isolated a cDNA for the reduced folate carrier (RFC-1) from human skin fibroblasts. A common polymorphism at position 80 in exon 2 of RFC-1 was identified. This polymorphism changes a guanine (G) to an adenine (A), abolishing a CfoI restriction site. Using genomic DNA samples from 169 healthy subjects, we identified 27.1% GG homozygotes, 21.9% AA homozygotes, and 50.9% GA heterozygotes. We explored the impact of this polymorphism, separately and in combination with the 677C->T polymorphism in the methylenetetrahydrofolate reductase gene, on folate status and total homocysteine levels. We found a moderate, but significant, increase in total homocysteine levels in doubly homozygous 80GG/677TT subjects as compared to 80GG/677CC (P = 0.01) or 80GG/677CT (P = 0.04) subjects. In addition, individuals who were 80AA/677CT had higher plasma folate levels than those who were 80GG/677CT (P = 0.02).
authors.affiliation: Laboratoire de Biochimie Médicale, INSERM U-308, France. achango@nctr.fda.gov
authors.forename: A
authors.initials: A
authors.lastname: Chango
authors.forename: N
authors.initials: N
authors.lastname: Emery-Fillon
authors.forename: G P
authors.initials: GP
authors.lastname: de Courcy
authors.forename: D
authors.initials: D
authors.lastname: Lambert
authors.forename: M
authors.initials: M
authors.lastname: Pfister
authors.forename: D S
authors.initials: DS
authors.lastname: Rosenblatt
authors.forename: J P
authors.initials: JP
authors.lastname: Nicolas
mesh_terms: D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D005492:Folic Acid / Q000097:blood*; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D017354:Point Mutation; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; C120043:SLC19A2 protein, human; D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)