Methylenetetrahydrofolate reductase 677C-->T variant modulates folate status response to controlled folate intakes in young women.
A common genetic variant in the methylenetetrahydrofolate reductase (MTHFR) gene involving a cytosine to thymidine (C-->T) transition at nucleotide 677 is associated with reduced enzyme activity, altered folate status and potentially higher folate requirements. The objectives of this study were to investigate the effect of the MTHFR 677 T allele on folate status variables in Mexican women (n = 43; 18-45 y) and to assess the adequacy of the 1998 folate U.S. Recommended Dietary Allowance (RDA), 400 micro g/d as dietary folate equivalents (DFE). Subjects (14 CC, 12 CT, 17 TT genotypes) consumed a low folate diet (135 micro g/d DFE) for 7 wk followed by repletion with 400 micro g/d DFE (7 CC, 6 CT, 9 TT) or 800 micro g/d DFE (7 CC, 6 CT, 8 TT) for 7 wk. Throughout repletion with 400 micro g/d DFE, the TT genotype had lower (P </= 0.05) serum folate and higher (P </= 0.05) plasma total homocysteine (tHcy) concentrations than the CC genotype. CT heterozygotes did not differ (P > 0.05) in their response relative to the CC genotype. Throughout repletion with 800 micro g/d DFE, the CT genotype had lower (P </= 0.05) serum folate concentrations and excreted less (P </= 0.05) urinary folate than the CC genotype. However, there were no differences (P > 0.05) in the measured variables between the TT and CC genotypes. Repletion with 400 micro g/d DFE led to normal blood folate and desirable plasma tHcy concentrations, regardless of MTHFR C677T genotype. Collectively, these data demonstrate that the MTHFR C-->T variant modulates folate status response to controlled folate intakes and support the adequacy of the 1998 folate U.S. RDA for all three MTHFR C677T genotypes.
Human Nutrition and Food Science Department, Cal Poly Pomona University, Pomona, CA 91768, USA.
Cheryl L
CL
Guinotte
Michael G
MG
Burns
Juan A
JA
Axume
Hiroko
H
Hata
Tania F
TF
Urrutia
Aaron
A
Alamilla
Dale
D
McCabe
Anny
A
Singgih
Edward A
EA
Cogger
Marie A
MA
Caudill
D000328:Adult; D001483:Base Sequence; D002140:California; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000097:blood / Q000378:metabolism; D017353:Gene Deletion; D014644:Genetic Variation; D005838:Genotype; D006630:Hispanic or Latino; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008487:Medical History Taking; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D018673:Nutrition Policy; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics* / Q000378:metabolism*; D013997:Time Factors; D014481:United States
D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)