MDR1polymorphisms are associated with inflammatory bowel disease in a cohort of Croatian IBD patients

Brinar, Marko; Čuković‐Čavka, Silvija; Božina, Nada; Ravić, Katja Grubelić; Markoš, Pave; Ladić, Agata; Cota, Marijana; Krznarić, Željko; Vucelić, Boris

doi:10.1186/1471-230x-13-57

Cited by 37 publications

(28 citation statements)

References 38 publications

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“…No 2677A allele was observed. This allele was also absent in another Croatian study, where healthy controls and inflammatory bowel disease patients were examined [32]. The results were not comparable to the two other studies.…”

Section: Croatiamentioning

confidence: 57%

Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations

Hubacek

2013

Drug Metabolism and Drug Interactions

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Inter-individual differences in genes for drug metabolising enzymes and drug transporters are important for understanding efficacy in drug therapy. These differences are important both for the timely estimation of the dosage that should be prescribed to a patient and for the detection of individuals who are prone to side effects from the drug at normal doses. This review summarises the literature concerning the gene variants within nine major drug metabolising enzymes and drug transporters (i.e., CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, and MDR-1) in the Middle European region. Notably, published data are not extensive, and most studies were performed on relatively low numbers of individuals. No country has a complete coverage of all genes. Two variants (C2677T/A and C3435T) within the multidrug resistance-1 (MDR-1) gene and variants within the CYP2C9 gene were analysed within most Slavic populations. Nevertheless, even from this incomplete coverage (where unexpectedly high variability was at times seen both between and within populations), it could be extrapolated that the variants within the drug metabolising enzyme genes are present in roughly the same frequencies as in neighbouring countries.

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Section: Croatiamentioning

confidence: 57%

Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations

Hubacek

2013

Drug Metabolism and Drug Interactions

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“…In addition, ABCB1 SNPs (G2677T/A and C3435T) are associated with refractory UC and CD and might play a role in the resistance of T cells to GC treatment. 84 Their good or poor prognosis could depend on the cases depicted above indicating that either MDR1 loss of function or over-expression can lead to the same phenotype depending on the pathophysiological mechanisms primarily involved.…”

Section: Introductionmentioning

confidence: 99%

MDR1 in immunity: friend or foe?

et al. 2018

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MDR1 is an ATP-dependent transmembrane transporter primarily studied for its role in the detoxification of tissues and for its implication in resistance of tumor cells to chemotherapy treatment. Several studies also report on its expression on immune cells where it plays a protective role from xenobiotics and toxins. This review provides an overview of what is known on MDR1 expression in immune cells in human, and its implications in different pathologies and their treatment options.

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“…Moreover, an animal study reported that mice deficient in mdr1a spontaneously developed colitis resembling human UC (Banner et al, 2004), whereas mice deficient for other transporters, such as MRP2 and BCRP, did not (Chu et al, 2006). In addition, several studies characterizing the association between MDR1 polymorphisms and IBD susceptibility (Brinar et al, 2013;Zhao et al, 2015) have indicated that stimulating P-gp expression and function could be a new treatment of IBD.…”

Section: Introductionmentioning

confidence: 99%

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

Jing

Safarpour

Zhang

et al. 2018

J Pharmacol Exp Ther

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Downregulation of P-glycoprotein (P-gp) is implicated in the pathophysiology of inflammatory bowel disease (IBD). Berberine, a principal isoquinoline alkaloid extracted from species, has been reported to exhibit therapeutic potential in IBD. In this study, we used a dextran sulfate sodium (DSS)-induced colitis rat model to evaluate the effect of berberine on P-gp and explore its mechanism of action. Berberine treatment improved DSS-induced colitis symptoms, attenuated inflammatory markers (myeloperoxidase, tumor necrosis factor-, and interleukin-1 and -6), and enhanced P-gp expression in a dose-dependent manner. Although colonic expression of the P-gp-related nuclear receptor pregnane X receptor and transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) were downregulated in the colitis model, gene and protein expression analysis revealed that berberine treatment reversed only the downregulation of Nrf2. In vitro studies using Caco-2 cells showed that the multidrug resistance 1 () gene and P-gp protein were upregulated by berberine in a dose- and time-dependent manner. Significant upregulation of the gene by berberine was abrogated by Nrf2 silencing, indicating that the Nrf2-mediated pathway was responsible for this activation. Luciferase assays showed a dose-dependent increase in Nrf2 reporter gene activity after berberine treatment in Caco-2 cells, with a significant 2-fold elevation at 2.5M berberine, suggesting that berberine is a strong Nrf2 activator. These results indicate the possible involvement of Nrf2-mediated upregulation of P-gp in the therapeutic effect of berberine on colitis and highlight the potential of P-gp and/or Nrf2 as new therapeutic targets for IBD.

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MDR1polymorphisms are associated with inflammatory bowel disease in a cohort of Croatian IBD patients

Cited by 37 publications

References 38 publications

Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations

Drug metabolising enzyme polymorphisms in Middle- and Eastern-European Slavic populations

MDR1 in immunity: friend or foe?

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

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