Association between a SLC23A2 Gene Variation, Plasma Vitamin C Levels, and Risk of Different Diseases
Journal of Advances in Medical and Pharmaceutical Sciences,
Background: Vitamin C is an important plasma water-soluble antioxidant that plays an essential role in the absorption of iron, detoxification of exogenous compounds, and remaking vitamin E for the protection of lipid membranes. In addition, vitamin C is essential in the synthesis of collagen. Vitamin C concentrations of plasma are determined by dietary intake and genetic factors. Ascorbic acid is the functional form of vitamin C, which is transported into the cell through sodium vitamin C transporters (SVCTs). There are two forms of SVCTs which are SVCT1 encoded by the SLC23A1 gene and SVCT2 encoded by the SLC23A2. The SLC23A2 gene locus on human chromosome 20P12. It expresses in most human tissues, except lung and skeletal muscle that it is important in regulating the intracellular concentration of ascorbic acid to protect the cell from oxidative stress and promote type 1 collagen maturation. Maintaining proper concentrations of plasma and cellular vitamin C concentration is important for the normal metabolic function of the body and preventing several diseases. In the contrast, a low concentration of vitamin C caused by SLC23A2 variation can cause several chronic diseases. Our systematic review discusses four diseases related to the variation of SLC23A2 gene and plasma vitamin C levels which are glaucoma, acute coronary syndrome among women, gastric cancer, and HPV16-associated head and neck cancer.
Methods: By using NCBI databases, specifically GenBank to analyze DNA sequence and mRNA sequence of SLC23A2 gene. GenBank file format was helpful to extract an accession number of the gene, number of amino acids, number of exons and introns, and length of nucleotides. FASTA format was also useful to retrieve the nucleotide sequence and get the function of the protein. BLAST was used to compare the protein product of the SLC23A2 gene between humans and Macaca mulatta (Rhesus monkey).
Results: the accession number of the SLC23A2 gene was NC_000020.11, the number of exons found was 18, and the gene was located in chromosome 20. This gene encodes one of the two required transporters, and the encoded protein accounts for tissue-specific uptake of vitamin C. This gene had an official symbol of SLC23A1. And they found a significant association between the single-nucleotide polymorphism (SNP) rs1279683 (A > G) in SLC23A2 and an increased risk of POAG in homozygous G allele (GG) carriers. Also, POAG patients with this SNP appear to have a significantly lower level of plasma vitamin C compared to other genotypes. Finally, many organisms have the same gene, such as dogs, mice, rats, and chickens.
Conclusion: there is a significant association between SLC23A2 gene mutation, increased risk for vitamin C deficiency, and several diseases. SNP in the SLC23A2 gene was significantly associated with a higher risk of POAG in GG allele carriers as well as lower plasma vitamin C concentration.
- SLC23A2 gene
- vitamin C
- ascorbic acid
- glaucoma and HPV16.
How to Cite
Dalgård C, Christiansen L, Vogel U, Dethlefsen C, Tjønneland A, Overvad K. Variation in the Sodium-Dependent Vitamin C Transporter 2 Gene Is Associated with Risk of Acute Coronary Syndrome among Women. PLoS ONE. 2013;8(8):e70421.
Erichsen H, Engel S, Eck P, Welch R, Yeager M, Levine M et al. Genetic Variation in the Sodium-dependent Vitamin C Transporters, SLC23A1, and SLC23A2 and Risk for Preterm Delivery. American Journal of Epidemiology. 2005;163(3):245-254.
Duell E, Lujan-Barroso L, Llivina C, Muñoz X, Jenab M, Boutron-Ruault M et al. Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort. Genes & Nutrition. 2013;8(6): 549-560.
Liang W, Johnson D, Ma L, Jarvis S. Regulation of the human vitamin C transporters expressed in COS-1 cells by protein kinase C. American Journal of Physiology-Cell Physiology. 2002;283(6): C1696-C1704.
Münger K, Baldwin A, Edwards K, Hayakawa H, Nguyen C, Owens M et al. Mechanisms of Human Papillomavirus-Induced Oncogenesis. Journal of Virology. 2004;78(21):11451-11460.
Chen A, Marsit C, Christensen B, Houseman E, McClean M, Smith J et al. Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer; 2009.
Kannan R, Stolz A, Ji Q, Prasad P, Ganapathy V. Vitamin C Transport in Human Lens Epithelial Cells: Evidence for the Presence of SVCT2. Experimental Eye Research. 2001;73(2):159-165.
Delcourt C, Korobelnik J, Barberger-Gateau P, Delyfer M, Rougier M, Le Goff M et al. Nutrition and age-related eye diseases: The Alienor (Antioxydants, lipides essentiels, nutrition et maladies oculaires) study. The journal of nutrition, health & aging. 2010;14(10):854-861.
Fernández-Martínez L, Letteboer S, Mardin C, Weisschuh N, Gramer E, Weber B et al. Evidence for RPGRIP1 gene as risk factor for primary open angle glaucoma. European Journal of Human Genetics. 2011;19(4):445-451.
Ford E, Ajani U, Croft J, Critchley J, Labarthe D, Kottke T et al. Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980–2000. New England Journal of Medicine. 2007;356(23):2388-2398.
HM Zhang, NW, OM, TY. Vitamin C inhibits the growth of a bacterial risk factor for gastric carcinoma: Helicobacter pylori [Internet]. Cancer. U.S. National Library of Medicine; 1997 [cited 2021Dec15]. Available:https://pubmed.ncbi.nlm.nih.gov/9366290/
Pal J, Sanal MG, Gopal GJ.Vitamin-C as anti-Helicobacter pylori agent: more prophylactic than curative- Critical review. Indian J Pharmacol; 2011.
Juan I. Young, Stephan Züchner, Gaofeng Wang Regulation of the Epigenome by Vitamin C, Annual Review of Nutrition. 2015;35(1):545-564.
Alexander J. Michels, Tory M. Hagen, Balz Frei Human Genetic Variation Influences Vitamin C Homeostasis by Altering Vitamin C Transport and Antioxidant Enzyme Function, Annual Review of Nutrition. 2013;33(1):45-70.
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