Polymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are associated with susceptibility to Crohn’s disease

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dc.contributor.authorAmir Shaghaghi, Mandana
dc.contributor.authorSerrano León, Alejandra
dc.contributor.authorEl-Gabalawy, Hani
dc.date.accessioned2015-05-25T15:14:04Z
dc.date.available2015-05-25T15:14:04Z
dc.date.issued2014
dc.description.abstractAbstract BACKGROUND: Crohn disease (CD) and ulcerative colitis (UC) are 2 common inflammatory bowel diseases (IBDs) associated with intestinal inflammation and tissue damage. Oxidative stress is suggested to play a major role in the initiation and progression of IBD. Vitamin C (ascorbate, ascorbic acid) supplementation has reduced oxidative stress in persons with IBD. The role of ascorbate transporters in IBD remains to be determined. SLC23A1 is a major ascorbate transporter in the intestinal tract, and some of its genetic variants have been associated with severely decreased ascorbate transport and lower systemic concentrations. OBJECTIVE: This study aimed to determine whether common genetic variants in the vitamin C transporter SLC23A1 are associated with the risk of IBD. DESIGN: Genomic DNA samples from patients with CD (n = 162) and UC (n = 149) from the Manitoba IBD Cohort Study and ethnically matched controls (n = 142) were genotyped for 3 SLC23A1 polymorphisms (rs6596473, rs33972313, and rs10063949) by using TaqMan assays. RESULTS: Variation at rs10063949 (G allele for heterozygote and homozygote) was associated with increased susceptibility to CD (OR: 2.54; 95% CI: 1.38, 4.66; OR: 4.72; 95% CI: 2.53, 8.81; P < 0.0001; respectively). A strong linkage disequilibrium (LD) was observed across the SLC23A1 region (variation rs6596473 with rs10063949) for CD and UC (D' = 0.94 and 0.96, respectively). The risk alleles confirmed a haplotype (CGG) that is carried more in CD patients (65.3%, P < 0.0001) than in controls (43.5%). CONCLUSIONS: A genetic variant (rs10063949-G) in the SLC23A1 ascorbate transporter locus was identified and is associated with an increased risk of CD in a white Canadian IBD cohort. The presented evidence that SLC23A1 variations can modulate the risk of CD has implications for understanding ascorbate transport in CD patients and provides a novel opportunity toward individualized nutritional therapy for patients carrying the disease-associated genotype.en_US
dc.identifier.citationAm J Clin Nutr. 2014 Feb;99(2):378-83.en_US
dc.identifier.doi10.3945/ajcn.113.068015
dc.identifier.urihttp://hdl.handle.net/1993/30527
dc.language.isoengen_US
dc.publisherAmerican Journal of Clinical Nutritionen_US
dc.relation.ispartofseries99(2);378-83
dc.rightsopen accessen_US
dc.subjectCrohnsen_US
dc.subjectNutritionen_US
dc.subjectBernsteinen_US
dc.subjectPolymorphismsen_US
dc.subjectSodium-independenten_US
dc.titlePolymorphisms in the sodium-dependent ascorbate transporter gene SLC23A1 are associated with susceptibility to Crohn’s diseaseen_US
dc.typeArticleen_US
dc.typeDataseten_US
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