Comparison of the genomic structure and variation in the two human sodium-dependent Vitamin C transporters, SLC23A1 and SLC23A2

Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Human Genetics (Impact Factor: 4.82). 10/2004; 115(4):285-94. DOI: 10.1007/s00439-004-1167-x
Source: PubMed


Vitamin C (L-ascorbic acid) is an essential co-factor for eight mammalian enzymes and quenches reactive oxygen species. Sodium-dependent vitamin C transport is mediated by two transporters, SVCT 1 and SVCT 2, encoded by SLC23A1 and SLC23A2. We characterized the genomic structures of SLC23A1 and SLC23A2, determined the extent of genetic variation and linkage disequilibrium across each gene, analyzed nucleotide diversity to estimate the effect of selective pressure, and compared sequence variation across species. In SLC23A1, the majority of single nucleotide polymorphisms (SNPs) are population-specific in either African Americans or Caucasians, including three of four non-synonymous SNPs. In contrast, most SNPs in SLC23A2 are shared between African Americans and Caucasians, and there are no non-synonymous SNPs in SLC23A2. Our analysis, combined with previous in vitro and in vivo studies, suggests that non-synonymous variation appears to be tolerated in SLC23A1 but not SLC23A2, and that this may be a consequence of different selective pressures following past gene duplication of the sodium-dependent vitamin C transporters. Genetic association studies of these two genes will need to account for the differences in haplotype structure and the population-specific variants. Our data represent a fundamental step toward the application of genetics to refining nutrient recommendations, specifically for vitamin C, and may serve as a paradigm for other vitamins.

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    • "In the present study, we showed that rs4987219 in intron 8 and the synonymous rs1110277 in exon 11 were associated with the severe acute leukopenia and stomatitis, respectively. In 2004, the genomic structure and variations in human SLC23A1 and SLC23A2 gene was clarified by Eck et al. 32. SLC23A2 gene was found to be 158,398 bp long, containing 17 exons, but several large introns resulted in transcript of 7,421 bp 32. "
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    • "Our study identified one SNP marker (and haplotypes) in association with GC risk from the SLC23A2 gene, the homologous gene found in rat gastric tissue. Little is known about the distribution of these proteins in humans, but the genes are highly conserved in humans and rodents, indicating a common ancestral gene (Eck et al. 2004; Savini et al. 2008). Little is known about the possible functions of the SNP markers for which we and others have observed associations (Chen et al. 2009; Erichsen et al. 2006; Wright et al. 2009; Skibola et al. 2008), but discrepancies across studies could also reflect different expression patterns for these genes in different tissues. "
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