Abstract
Background: The MTHFR 677C→T variant is associated with reduced enzyme activity, abnormalities of folate metabolism, and potential increase in folate requirement. The effect of this variant on the Recommended Dietary Allowance (RDA) for folate is unclear.Objective: The aim of this study was to assess the effect of the MTHFR 677C→T polymorphism on the current folate RDA for US adults aged ≥19 y (400 μg/d) by race and ethnicity.Design: We calculated the projected RDA for folate for each racial and ethnic group according to the methods of the Institute of Medicine. We modeled the projected RDA with different hypothetical effect sizes ranging from 5% to 50%. The RDA value was then weighted according to the US prevalence of the TT (or the combined CT/TT) genotype in each racial and ethnic group.Results: The projected RDA ranges were based on TT genotype frequencies and on different effect sizes (5–50%) that ranged from 400 to 421 μg/d for non-Hispanic whites, 401–436 μg/d for Mexican Americans, and 400–402 μg/d for non-Hispanic blacks.Conclusions: Our findings suggest that the current RDA for folate differs little for non-Hispanic whites, non-Hispanic blacks, and Mexican Americans irrespective of the MTHFR TT genotype, and, from a population perspective, the MTHFR 677C→T variant does not warrant modifications to the current RDA for dietary folate at this time.
Highlights
Disturbances in the folate metabolism pathway are associated with a wide range of conditions, and variants from genes involved in this pathway may play a role in the genesis of these conditions [1–7]
Data from the our calculations suggest that the current Recommended Dietary Allowance (RDA) for dietary folate differs little for non-Hispanic whites, non-Hispanic blacks, and Mexican Americans irrespective of the presence of the MTHFR TT genotype
Findings from this study suggest that, from a population perspective, the MTHFR 677C/T variant does not warrant modifications to the current RDA for dietary folate on the basis of a hypothesis that revision would be warranted if genetic variations increased the RDA by 25%
Summary
Disturbances in the folate metabolism pathway are associated with a wide range of conditions, and variants from genes involved in this pathway may play a role in the genesis of these conditions [1–7]. The frequency of the TT genotype varies across racial and ethnic groups and is most common among Hispanics, followed by non-Hispanic whites and nonHispanic blacks [12]. Individuals homozygous for this variant have a mean MTHFR activity that is ,50% of the MTHFR activity of CC individuals, whereas heterozygous individuals have shown intermediate values of activity [13, 14]. The MTHFR 677C/T variant is associated with reduced enzyme activity, abnormalities of folate metabolism, and potential increase in folate requirement The effect of this variant on the Recommended Dietary Allowance (RDA) for folate is unclear.
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