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P-glycoprotein expression in Helicobacter pylori-positive patients: the influence of MDR1 C3435T polymorphism
Marhanis Omar1, Andrew Crowe, Richard Parsons
1School of Pharmacy, Curtin University, PO Box U1987, Perth, WA 6845, Australia. m.omar3@postgrad.curtin.edu.au
Objective:
The aim of this study was to determine whether the presence of Helicobacter pylori (H. pylori) infection and multidrug resistance protein 1 (MDR1) C3435T polymorphism had an influence on P-glycoprotein (P-gp) expression in the upper gastrointestinal tract.
Methods:
A total of 76 patients who underwent upper gastroendoscopy at Sir Charles Gairdner Hospital in Western Australia from October 2010 to July 2011 were enrolled in the study. Antral and duodenal biopsies were collected for P-gp examination. Blood samples were taken and analyzed for MDR1 C3435T polymorphism. H. pylori infection status was confirmed by culture and polymerase chain reaction.
Results:
A significant difference was found in P-gp expression between H. pylori-positive and H. pylori-negative patients (P = 0.028). For the MDR1 C3435T polymorphism, the TT genotype had a significantly lower P-gp expression compared with the CC genotype in antral specimens (P = 0.041). The homozygous TT genotype with H. pylori infection was also significantly different in P-gp expression compared with H. pylori-negative patients (P = 0.029).
Conclusions:
P-gp expression in the upper gastrointestinal tract is associated with H. pylori infection, and the TT genotype appeared to be associated with lower P-gp expression than the CC genotype in the stomach.
Insights
Helicobacter pylori infection and MDR1 C3435T gene variations influence P-glycoprotein expression in the upper gut. The TT genotype showed lower P-gp levels, especially with H. pylori infection.
Area of Science:
- Gastroenterology
- Pharmacogenomics
- Infectious Diseases
Background:
- P-glycoprotein (P-gp) is a key efflux transporter in the upper gastrointestinal tract.
- Its expression can be influenced by genetic factors and infections.
- Understanding these influences is crucial for drug absorption and efficacy.
Purpose of the Study:
- To investigate the impact of Helicobacter pylori (H. pylori) infection on P-gp expression.
- To determine the role of the multidrug resistance protein 1 (MDR1) C3435T polymorphism in P-gp expression.
- To assess the combined effect of H. pylori infection and MDR1 genotype on P-gp levels.
Main Methods:
- Upper gastrointestinal biopsies and blood samples were collected from 76 patients.
- P-gp expression was analyzed in antral and duodenal biopsies.
- H. pylori infection status was confirmed using culture and PCR.
- MDR1 C3435T polymorphism was genotyped.
Main Results:
- H. pylori infection significantly altered P-gp expression (P=0.028).
- The TT genotype of MDR1 C3435T showed significantly lower P-gp expression compared to the CC genotype in antral tissues (P=0.041).
- A significant difference in P-gp expression was observed in patients with the TT genotype and H. pylori infection compared to H. pylori-negative patients (P=0.029).
Conclusions:
- H. pylori infection is associated with altered P-gp expression in the upper gastrointestinal tract.
- The TT genotype of the MDR1 C3435T polymorphism is linked to reduced P-gp expression in the stomach.
- These findings highlight the interplay between infection, genetic variations, and drug transporter expression.
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