Association between a SLC23A2 Gene Variation, Plasma Vitamin C Levels, and Risk of Different Diseases

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.