A polymorphism (80G-> A) in the reduced folate carrier gene and its associations with folate status and homocysteinemia

5-Methyltetrahydrofolate is the predominant form of folate in plasma. It ma y 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 w as identified. This polymorphism changes a guanine (G) to an adenine (A), a bolishing a CfoI restriction site. Using genomic DNA samples from 169 healt hy subjects, we identified 27.1% GG homozygotes, 21.9% AA homozygotes, and 50.9% GA heterozygotes. We explored the impact of this polymorphism, separa tely and in combination with the 677C->T polymorphism in the methylenetetra hydrofolate reductase gene, on folate status and total homocysteine levels. We found a moderate, but significant, increase in total homocysteine level s 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 mere 8 0AA/677CT had higher plasma folate levels than those who were 80GG/677CT (P = 0.02). (C) 2000 Academic Press.