Human Genetic Variation Influences Vitamin C Homeostasis by Altering Vitamin C Transport and Antioxidant Enzyme Function

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331
Annual Review of Nutrition (Impact Factor: 8.36). 04/2013; 33(1). DOI: 10.1146/annurev-nutr-071812-161246
Source: PubMed


New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk. Expected final online publication date for the Annual Review of Nutrition Volume 33 is July 17, 2013. Please see for revised estimates.

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    • "Most mammals are capable of de novo hepatic synthesis of Asc from glucose, through a biosynthetic pathway that employs the enzyme L-gulono-γ-lactone oxidase (GULO) for the terminal oxidation reaction [14] [15] [16] [17]. However, higher primates (including humans), guinea pigs, and some bats are obligatorily dependent on dietary sources of the vitamin [18] [19]. This requirement is due to an inactivation of the GULO gene [14] [15] [20]. "
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