Genetic Variation in Human Vitamin C Transporter Genes in Common Complex Diseases

Abstract

Adequate plasma, cellular, and tissue vitamin C concentrations are required for maintaining optimal health through suppression of oxidative stress and optimizing functions of certain enzymes that require vitamin C as a cofactor. Polymorphisms in the vitamin C transporter genes, compromising genes encoding sodium-dependent ascorbate transport proteins, and also genes encoding facilitative transporters of dehydroascorbic acid, are associated with plasma and tissue cellular ascorbate status and hence cellular redox balance. This review summarizes our current knowledge of the links between variations in vitamin C transporter genes and common chronic diseases. We conclude that emerging genetic knowledge has a good likelihood of defining future personalized dietary recommendations and interventions; however, further validations through biological studies as well as controlled dietary trials are required to identify predictive and actionable genetic biomarkers. We further advocate the need to consider genetic variation of vitamin C transporters in future clinical and epidemiologic studies on common complex diseases.

Clinical and Vitamin Response to a Short‐Term Multi‐Micronutrient Intervention in Brazilian Children and Teens: From Population Data to Interindividual Responses

“…These results may be due to combinations of dietary recall bias, differences in bioavailability of nutrients due to interindividual variation in transport (e.g., ref. []) or metabolism of micronutrients (e.g., ref. []), differences in microbiomes of individuals (e.g., ref.…”

GutSelf: Interindividual Variability in the Processing of Dietary Compounds by the Human Gastrointestinal Tract

“…Therefore, it can be assumed that genetic alterations in SLC23A1 and SLC23A2 will have a substantial effect on human vitamin C status. However, SLC23A1 knockout mice are still capable of absorbing ascorbic acid from the diet, but pharmacokinetics and viability of the offspring is severely affected . Although 1440 and 8165 variations of SVCT1 and SVCT2, respectively, are listed in the SNP database, not many of them have been verified in different populations, and most of them have neither been reported in the literature nor functionally characterized ( Table ) .…”

“…However, SLC23A1 knockout mice are still capable of absorbing ascorbic acid from the diet, but pharmacokinetics and viability of the offspring is severely affected . Although 1440 and 8165 variations of SVCT1 and SVCT2, respectively, are listed in the SNP database, not many of them have been verified in different populations, and most of them have neither been reported in the literature nor functionally characterized ( Table ) . Whereas nearly all SNPs in SLC23A2 are shared between African Americans and Caucasians, a substantial number of SNPs in SLC23A1 are population specific in either Caucasians or African Americans.…”

Una mirada actual de la vitamina C en salud y enfermedad

“…El gen de SVCT2, por su parte, está situado en el cromosoma 20 (20p12.2), presenta 17 exones y supera en 10 veces el tamaño del gen de SVCT1 y el número de SNPs que presenta 7 . Algunos SNPs encontrados en los exones 8 y 11 y en los intrones 2 y 3 de SVCT2 se han asociado con susceptibilidad a parto prematuro, cáncer de cuello y del tracto digestivo 45,51 . Se postula que las variantes genéticas de SVCT2 podrían influir en los niveles de AA intracelular, en la síntesis de colágeno y/o en la defensa antioxidante 51,52 .…”

“…Algunos SNPs encontrados en los exones 8 y 11 y en los intrones 2 y 3 de SVCT2 se han asociado con susceptibilidad a parto prematuro, cáncer de cuello y del tracto digestivo 45,51 . Se postula que las variantes genéticas de SVCT2 podrían influir en los niveles de AA intracelular, en la síntesis de colágeno y/o en la defensa antioxidante 51,52 . Por otro lado, los SNPs en proteínas relacionadas con el reciclaje del AA también se asocian con niveles reducidos de vitamina C, como el homocigoto para el alelo Hp2 de la haptoglobina y el genotipo GSTM1-nulo de la glutatión-S-transferasa 53 .…”