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

Abstract

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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