The SLC2A14 gene, encoding the novel glucose/dehydroascorbate transporter GLUT14, is associated with inflammatory bowel disease

Abstract

Background: 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 (SLC2A14) 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. Objective: This study aimed to determine the substrate(s) for the GLUT14 protein and interrogated genetic associations of SLC2A14 with IBD. Design: The uptake of radiolabeled substrates into Xenopus laevis 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 SLC2A14 gene. Results: Both GLUT14 isoforms mediated the uptake of dehydroascorbic acid and glucose into X. laevis oocytes. Three alleles in the SLC2A14 gene associated independently with IBD. The odds of having ulcerative colitis (UC) or Crohn disease (CD) were elevated in carriers of the SLC2A14 SNP rs2889504-T allele (OR: 3.60; 95% CI: 1. 95, 6.64 and OR: 4.68; 95% CI: 2.78, 8.50, respectively). Similarly, the SNP rs10846086-G 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 rs12815313-T 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). Conclusion: 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.Am J Clin Nutr 2017;106:1508-13.

A six‑gene support vector machine classifier contributes to the diagnosis of pediatric septic shock

“…Previous studies have revealed that genetic variations in Slc2a14 are involved in the development and progression of chronic diseases, including inflammatory bowel disease (IBD) and Alzheimer's disease (37-39). The facilitated glucose transporter 14 encoded by SLC2A14 promotes the development of IBD and may be applied for precision intervention of IBD (38). SLP-2 belongs to the stomatin protein family, plays a critical role in T cell activation and is a candidate target for immunomodulation (40).…”

Chemical biology probes of mammalian GLUT structure and function

“…GLUT3 is mainly present in the brain [ 11 ]. A GLUT3 variant (GLUT14) has also been found in the genome as a duplicon of GLUT3 [ 12 ], but is essentially uncharacterised and of unknown function and tissue distribution, although there is some disease association [ 13 ]. GLUT2 and GLUT3 have K m values for glucose transport that are higher and lower, respectively, than fasting blood glucose reflecting the functions of these proteins in supplying glucose (GLUT2) and rapidly and avidly removing glucose (GLUT3) from the circulation.…”

Keratinocytes Derived from Patient-Specific Induced Pluripotent Stem Cells Recapitulate the Genetic Signature of Psoriasis Disease

“…However, other glucose transporters, including SLC2A10 (GLUT10) and SLC2A14 (GLUT14), were significantly downregulated. A previous study hypothesized that genetic variations in SLC2A14 may be associated with inflammatory disease [73]. Also, SLC2A10 was found to be associated with T2D [74,75].…”