Solute carrier family 2, facilitated glucose transporter member 14
dehydroascorbic acid transmembrane transporter activity
The <i>SLC2A14</i> gene, encoding the novel glucose/dehydroascorbate transporter GLUT14, is associated with inflammatory bowel disease.
<b>Background:</b> Variations in intestinal antioxidant membrane transporters are implicated in the initiation and progression of inflammatory bowel disease (IBD). Facilitated glucose transporter member 14 (GLUT14), encoded by the solute carrier family 2 member 14 (<i>SLC2A14</i>) gene, is a putative transporter for dehydroascorbic acid and glucose. Although information on the gene is limited, shorter and longer GLUT14 isoforms have been identified. We hypothesized that GLUT14 mediates glucose and dehydroascorbic acid uptake. If this function could be validated, then genetic variations may associate with IBD.<b>Objective:</b> This study aimed to determine the substrate(s) for the GLUT14 protein and interrogated genetic associations of <i>SLC2A14</i> with IBD.<b>Design:</b> The uptake of radiolabeled substrates into <i>Xenopus laevis</i> oocytes expressing the 2 GLUT14 isoforms was assessed. Examination of gene-targeted genetic association in the Manitoba Inflammatory Bowel Disease Cohort Study was conducted through the genotyping of single nucleotide polymorphisms (SNPs) representing linkage blocks of the <i>SLC2A14</i> gene.<b>Results:</b> Both GLUT14 isoforms mediated the uptake of dehydroascorbic acid and glucose into <i>X. laevis</i> oocytes. Three alleles in the <i>SLC2A14</i> gene associated independently with IBD. The odds of having ulcerative colitis (UC) or Crohn disease (CD) were elevated in carriers of the <i>SLC2A14</i> SNP <i>rs2889504-T</i> allele (OR: 3.60; 95% CI: 1.95, 6.64 and OR: 4.68; 95% CI: 2.78, 8.50, respectively). Similarly, the SNP <i>rs10846086-G</i> allele was associated with an increased risk of both UC and CD (OR: 2.91; 95% CI: 1.49, 5.68 and OR: 3.00; 95% CI: 1.55, 5.78, respectively). Moreover, the SNP <i>rs12815313-T</i> allele associated with increased susceptibility to CD and UC (OR: 2.12; 95% CI: 1.33, 3.36 and OR: 1.61; 95% CI: 1.01, 2.57, respectively).<b>Conclusion:</b> These findings strengthen the hypothesis that genetically determined local dysregulation of dietary vitamin C or antioxidants transport contributes to IBD development. These transporter proteins are targetable by dietary interventions, opening the avenue to a precision intervention for patients of specific genotypes with IBD. This trial was registered at clinicaltrials.gov as NCT03262649.