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Effect of the MTHFR 677C→T polymorphism on folate status response to folic acid doses in large‐scale randomized intervention trial in young Chinese women

The study objective was to evaluate the effect of the MTHFR677C→T polymorphism on folate status response to different daily or weekly folic acid (FA) doses in young women. Women (N=1108) were randomly assigned for 6 mo FA interventions to 1 of 6 groups (100 μg 1 X daily, 25 μg 4 X daily, 400 μg 1 X daily, 100 μg 4 X daily, 4,000 μg 1 X daily, or 4,000 μg once weekly). At baseline, plasma folate did not differ (p=0.448) among MTHFR677C→T genotype groups; however, homocysteine (Hcy) was 13.5% higher (p<0.001) in women with the TT genotype compared to the CC genotype. Genotype effect on plasma folate response to FA supplementation was evident by comparing the % increase from baseline to 6 mo in subjects with the CC vs TT genotype (100 μg/day 152% CC vs 80% TT; 400 μg/day 267% CC vs 221% TT; 4,000 μg/day 441% CC vs 396% TT). For CC genotypes, no change in Hcy was observed at 6 mo among women who took 100 μg/day FA in contrast to 14.6% and 15.7% reductions for 400 μg/day and 4,000 μg/day groups, respectively. For TT genotypes, the corresponding reductions in Hcy were 6.4%, 22.8%, and 31.5% respectively. At 6 mo, Hcy was not different (p>0.05) between women with CC and TT genotypes regardless of FA dose. These results indicate that plasma folate increased more and Hcy decreased less among women with the MTHFR 677 CC genotype compared to women with TT genotype in response to FA supplementation. This work was supported by a collaborative CDC agreement.