Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

P-glycoprotein is important in local antibiotic resistance. Aim was to evaluate the role of P-glycoprotein in local antibiotic resistance in patients with antral gastritis during antibiotic therapy to Helicobacter pylori infection. In the group of 53 patients with pathohistologically verified gastritis and microbiologically confirmed H. pylori infection (no signs of antimicrobial resistance) we have determined P-glycoprotein activity in gastric mucosa biopsy specimens, and compared them with the P-glycoprotein activity in 12 control subjects with normal endoscopic findings. The H. pylori positive patients were treated according to Maastricht protocol with short-term 7-day therapy consisting of two antibiotics (amoxicillin and azithromycin/metronidazole and clarithromycin) and a proton pump inhibitor P-glycoprotein activity was determined in rhodamine dye efflux test and quantified by ratio of the mean fluorescence (RMF) in flow cytometry analysis. H. pylori was successfully eradicated in the first cycle in 20 patients, whereas therapy was continued in 33 patients. The mean pre-treatment RMF values were higher in patients with H. pylori infection then in control subjects (p < 0.0046). RMF was also higher in patients with multiple therapeutic failure than in those with successful H. pylori eradication (p < 0.0001). RMF increased significantly during the antibiotic therapy (p < 0.05). P-glycoprotein might be one of the causes of therapy failure in patients with H. pylori. Our study confirms the importance of quantitative evaluation of P-glycoprotein expression during antibiotic treatment response.
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PMID:The importance of P-glycoprotein multidrug transporter activity measurement in patients with Helicobacter pylori infection. 2010 60

The functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the ABCB1 gene encoding the xenobiotic transporter P-glycoprotein (P-gp) may influence susceptibility to several diseases, as well as the clinical outcome of treatment with P-gp substrates. Exposure to environmental chemicals is thought to be involved in peptic ulcer pathogenesis and then later in stomach cancer development. About 80% of ulcers are associated with Helicobacter pylori infection, one of the risk factors of stomach cancer. P-gp-transported drugs are used in treatment of H. pylori. Therefore, a lack of effectiveness in eradication therapy can lead to chronic stomach inflammation and promote cancerogenesis. In this study, 196 patients with peptic ulcers divided into two groups with and without H. pylori infection and combined with 96 healthy controls were genotyped for the ABCB1 C3435T SNP. A trend towards higher incidence of the 3435TT genotype among peptic ulcer patients than in controls (p = 0.0983) was observed. Likewise, the 3435T allele was more frequent in groups suffering from peptic ulcers. The association was near to statistical significance (p = 0.0538). Between analyzed genotypes and H. pylori infection, statistically significant dependence was found (p = 0.0372). In addition, the CT genotype was associated with 1.56 times and the TT with 2.45 times higher prevalence of infection compared to the CC genotype. Asimilar association was present in a subgroup of peptic ulcer men (p = 0.0090). The isolated C3435T ABCB1 SNP is not a major factor for genetic susceptibility to peptic ulcer, but in a group of men who suffered from peptic ulcer, this polymorphism seemed to be a risk factor for H. pylori infection development.
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PMID:C3435T polymorphism of the ABCB1 gene: impact on genetic susceptibility to peptic ulcers. 2200 87

One of the most common malignant diseases, both worldwide and in Poland, is gastric cancer. The pathogenesis of gastric cancer development is not entirely clear. Next to the environmental risk factors, such as Helicobacter pylori infection or dietary habits, the host genetic factors as predispositions to gastric cancer development are discussed. A transmembrane protein that could be associated with predisposition to cancer development is P-glycoprotein (P-gp). Physiologically, P-gp is present in normal tissue of the gastrointestinal tract, where it plays a protective role by transporting xenobiotics from a cell into extracellular environment. P-gp is encoded by the highly polymorphic ABCB1 gene. The most frequent polymorphisms at positions 1236, 2677, and 3435 may affect both the function and amount of protein, thereby leading to a loss of its physiological function, which could increase the predisposition to development of many diseases, including cancer. In this study, the potential significance of the ABCB1 gene in the development and progression of gastric cancer was evaluated. In 19 tissue samples collected from patients with gastric cancer, the ABCB1 gene polymorphisms were identified at positions 1236 and 2677 by automated sequencing and SNP 3435 by the RFLP method. The relative level of ABCB1 expression was measured in 10 samples of gastric cancer and morphologically normal tissues by real-time PCR. For SNPs at positions 1236, 2677, and 3435, no statistically significant differences in genotype frequencies between gastric cancer patients and healthy individuals were found. However, genotype TT for all studied polymorphisms occurred more frequently in the group of gastric cancer patients (31.6, 26.3, 42.1%, respectively) than in the group of healthy individuals (14.6, 13.5, 21.9%, respectively). The lowest relative expression levels of ABCB1 mRNA were observed for genotypes CC of SNP 1236, CC of SNP 3435, and GG of SNP 2677 (median: 0.215, 0.160, 0.160, respectively). There was a tendency that mutant homozygote TT for SNPs at positions 1236, 2677, and 3435 occurred more frequently in the subgroup of patients with Tis or stage I of TNM classification (SNP 1236 p = 0.0760; SNP 2677 p = 0.0813; SNP 3435 p = 0.0760) than in the subgroup of patients with stage II or III. Also the expression levels were lowest (median 0.740) in the group of patients with the less advanced clinical stage of cancer (Tis or I). Preliminary research showed that the ABCB1 gene polymorphisms at positions 1236, 2677, and 3435 were not related to an increased susceptibility of gastric cancer development. However, they may be associated with the inhibition of gastric cancer progression.
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PMID:Is the ABCB1 gene associated with the increased risk of gastric cancer development?--preliminary research. 2523 28