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Does the MTHFR 677CT variant affect the Recommended Dietary Allowance for folate in the US population?^1,2,3,4

¹ From the National Center on Birth Defects and Developmental Disabilities (JR, HCH, and MEC) and Office of Public Health Genomics (QY), Centers for Diseases Control and Prevention, Atlanta, GA, and the Department of Food Science and Nutrition, Laval University, Quebec City, Canada (JR).

² The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

³ Supported in part by a Fellowship in Genetics and the Public Health Research and Practice Program, which are jointly sponsored by the Centers for Disease Control and the American Society of Human Genetics (JR), and by a fellowship award from the Canadian Institutes of Health and Research (JR).

⁴ Reprints not available. Address correspondence to J Robitaille, Department of Food Science and Nutrition, Laval University, Pavillon des Services, 2440 Hochelaga Boulevard, Room 2751, Quebec, PQ G1V 0A6, Canada. E-mail: julie.robitaille{at}fsaa.ulaval.ca.

ABSTRACT

Background: The MTHFR 677CT 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 677CT 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 677CT variant does not warrant modifications to the current RDA for dietary folate at this time.

Received for publication November 26, 2008. Accepted for publication January 26, 2009.