Literature DB >> 20376628

Effects of CYP2C19, MDR1, and interleukin 1-B gene variants on the eradication rate of Helicobacter pylori infection by triple therapy with pantoprazole, amoxicillin, and metronidazole.

Barbara Gawrońska-Szklarz1, Andrzej Siuda, Mateusz Kurzawski, Dariusz Bielicki, Wojciech Marlicz, Marek Droździk.   

Abstract

OBJECTIVE: Eradication of H. pylori is an important treatment strategy in peptic ulcer patients. Current regimens of eradication consist of proton pump inhibitor (PPI) and two antibiotics. Effects of PPI may depend on their metabolism, and other factors important for the pathophysiology of peptic ulcer disease. Aim of the present study was to evaluate an association of CYP2C19, MDR1, and IL-1B polymorphisms with the eradication rate of H. pylori in Polish Caucasian patients treated with a triple therapy of pantoprazole, amoxicillin, and metronidazole.
METHODS: A total of 139 peptic ulcer patients, positive for H. pylori infection, were treated with triple therapy (pantoprazole + amoxicillin + metronidazole). Subsequently, the patients were divided into two groups (group 1, success, and group 2, failure of eradication after therapy) and genotyped by the PCR-RFLP method for the presence of CYP2C19 variant alleles (*2, *3, and *17), and MDR1 3435C>T and IL-1B +3954C>T polymorphisms. Pantoprazole serum concentrations were measured using the HPLC method.
RESULTS: No significant differences in frequency or distribution of CYP2C19 genotypes were found between the two groups of patients (i.e., with successful H. pylori eradication and treatment failure). However, any carrier of defective CYP2C19*2/*2 genotype was found among patients with treatment failure. Similarly, MDR1 and IL-1B genotypes were found to be significantly associated with the success or failure of H. pylori eradication. Univariate and multivariate analysis of the genotypes did not reveal any significant association between the genotypes and H. pylori eradication. Pantoprazole concentrations differed significantly, and were the highest in patients with defective allele CYP2C19*2 carriers and lowest in hyperactive genotype homozygotes CYP2C19*17/*17.
CONCLUSION: The results suggest that the CYP2C19 genotype contrary to MDR1 and IL-1B genotypes may have an impact on the efficacy of H. pylori eradication in peptic ulcer patients treated with pantoprazole in Polish Caucasian peptic ulcer patients administered pantoprazole, amoxicillin, and metronidazole.

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Year:  2010        PMID: 20376628     DOI: 10.1007/s00228-010-0818-1

Source DB:  PubMed          Journal:  Eur J Clin Pharmacol        ISSN: 0031-6970            Impact factor:   2.953


  31 in total

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8.  Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: effects of contents of these two forms in individual human samples.

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10.  Effect of MDR1 C3435T polymorphism on cure rates of Helicobacter pylori infection by triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP 2C19 genotypes and 23S rRNA genotypes of H. pylori.

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  11 in total

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3.  CYP2C19 polymorphism affects single-dose pharmacokinetics of oral pantoprazole in healthy volunteers.

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4.  PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19.

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6.  The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors.

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7.  The effect of MDR1 C3435T polymorphism on the eradication rate of H. pylori infection in PPI-based triple therapy: A meta-analysis.

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10.  Host Genetic Determinants Associated With Helicobacter pylori Eradication Treatment Failure: A Systematic Review and Meta-analysis.

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Journal:  Gastroenterology       Date:  2021-08-03       Impact factor: 22.682

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