Association of SLC22A4/5 Polymorphisms with Steroid Responsiveness of Inflammatory Bowel Disease in Japan

Nakahara, Seiya; Arimura, Yoshiaki; Saito, Katsuhiko; Gotō, Akira; Motoya, Satoshi; Shinomura, Yasuhisa; Miyamoto, Atsushi; Imai, Kohzoh

doi:10.1007/s10350-008-9208-5

Cited by 12 publications

(9 citation statements)

References 27 publications

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“…Polymorphisms in OCTN transporters are associated not only with the incidence of inflammatory bowel disease, but also with the pharmacological response to therapy. The Ϫ368 TϾG polymorphism in the SLC22A5 promoter corresponds to steroid resistance and inadequate response of Japanese patients with inflammatory bowel disease (Nakahara et al, 2008). These data suggest linkage between inflammatory bowel disease and SLC22A4 and SLC22A5 variants among different ethnic groups.…”

Section: Apical Uptake Transporters In the Intestinementioning

confidence: 76%

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

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Section: Apical Uptake Transporters In the Intestinementioning

confidence: 76%

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

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“…In a Japanese study, the association of SLC22A4=5 with steroid responsiveness of IBD was investigated (Nakahara et al, 2008). The CG haplotype, comprising the C allele of the À446C > T and À368T > G in SLC22A5 appeared to be a predictor of steroid resistance in Japanese patients with CD.…”

mentioning

confidence: 99%

Involvement of NAD(P)H:Quinone Oxidoreductase 1 and Superoxide Dismutase Polymorphisms in Ulcerative Colitis

Kosaka

Yoshino

Inui

et al. 2009

DNA and Cell Biology

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Inflammatory bowel disease is a multifactorial disease. Oxidative stress has been thought to be one of etiologic factor for inflammatory bowel disease. The genes superoxide dismutase (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are involved in inflammation and oxidative stress. The purpose of the present case-control study with 134 patients with ulcerative colitis (UC) and 125 healthy controls was to determine whether polymorphisms of these genes, the NQO1 C609T and the SOD2 Ala-9Val, are associated with the risk of UC and influence the clinical characteristics. These polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphisms and direct sequencing. In patients showing steroid resistance, the number with the NQO1 T/T genotype was significantly higher than other genotypes (odds ratio 9.45, 95% confidence interval 2.46-41.6, p = 0.002). In the patients whose onset of UC was age 20 years or younger, more patients had SOD2 T/T genotype than the other genotypes (odds ratio 6.46, 95% confidence interval 0.82-51.0). No association between these polymorphisms and UC risk was apparent. The NQO1 C609T polymorphism may influence steroid resistance of UC patients, while the SOD2 Ala-9Val polymorphism may influence age of onset of UC. Oxidative stress may influence the clinical features of UC.

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“…Variations in the solute carrier family 2 (SLC) genes SLC23A1 (9), SLC22A23 (10,11), and SLC22A4/SLC22A5 (12)(13)(14)(15), and ATP binding cassette subfamily B member 1 (ABCB1) (16)(17)(18) have been associated with IBD. They encode for intestinal membrane transporters of antioxidants, and it was hypothesized that genetically determined dysregulation of dietary antioxidants, prominently vitamin C, may contribute to IBD (9,19,20).…”

Section: Introductionmentioning

confidence: 99%

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

Shaghaghi

Zhouyao

et al. 2017

The American Journal of Clinical Nutrition

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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.

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Association of SLC22A4/5 Polymorphisms with Steroid Responsiveness of Inflammatory Bowel Disease in Japan

Cited by 12 publications

References 27 publications

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

Involvement of NAD(P)H:Quinone Oxidoreductase 1 and Superoxide Dismutase Polymorphisms in Ulcerative Colitis

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

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