Mandana Amir Shaghaghi1, Charles N Bernstein, Alejandra Serrano León, Hani El-Gabalawy, Peter Eck. 1. From Human Nutritional Sciences (MAS, ASL, and PE), The Richardson Centre for Functional Foods and Nutraceuticals (MAS, ASL, and PE), the IBD Clinical and Research Centre (CNB), and the Department of Internal Medicine (CNB and HE-G), University of Manitoba, Winnipeg, Canada.
Abstract
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.
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 CDpatients (65.3%, P < 0.0001) than in controls (43.5%). CONCLUSIONS: A genetic variant (rs10063949-G) in the SLC23A1ascorbate 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 CDpatients and provides a novel opportunity toward individualized nutritional therapy for patients carrying the disease-associated genotype.
Authors: Mandana Amir Shaghaghi; Haonan Zhouyao; Hongbin Tu; Hani El-Gabalawy; Gary H Crow; Mark Levine; Charles N Bernstein; Peter Eck Journal: Am J Clin Nutr Date: 2017-09-27 Impact factor: 7.045
Authors: Veedamali S Subramanian; Subrata Sabui; Ganapathy A Subramenium; Jonathan S Marchant; Hamid M Said Journal: Am J Physiol Gastrointest Liver Physiol Date: 2018-04-06 Impact factor: 4.052