Duodenal ulcer promoting gene of Helicobacter pylori

Gastroenterology. 2005 Apr;128(4):833-48. doi: 10.1053/j.gastro.2005.01.009.


Background & aims: Identification of a disease-specific H pylori virulence factors predictive of the outcome of infection remains unachieved.

Methods: We used the polymerase chain reaction and Southern blot to compare the presence of 14 vir homologue genes with clinical presentation of H pylori infection, mucosal histology, and mucosal interleukin (IL)-8 levels.

Results: We examined 500 H pylori strains from East Asia and South America, including 120 with gastritis, 140 with duodenal ulcer (DU), 110 with gastric ulcer (GU), and 130 with gastric cancer. Only 1 gene that encompassed both jhp0917 and jhp0918 called dupA (duodenal ulcer promoting gene) was associated with a specific clinical outcome. dupA was present in 42% of DU vs. 21% of gastritis (adjusted odds ratio [OR] = 3.1, 95% confidence interval [CI]: 1.7-5.7). Its presence was also associated with more intense antral neutrophil infiltration and IL-8 levels and was a marker for protection against gastric atrophy, intestinal metaplasia, and gastric cancer (OR for gastric cancer = 0.42, 95% CI: 0.2-0.9 compared with gastritis). In vitro studies in gastric epithelial cells using dupA -deleted and -complemented mutants showed that the dupA plays roles in IL-8 production, in activation of transcription factors responsible for IL-8 promoter activity, and in increased survivability at low pH.

Conclusions: dupA is a novel marker associated with an increased risk for DU and reduced risk for gastric atrophy and cancer. Its association with DU-promoting and -protective effects against atrophy/cancer was evident in both Asian and Western countries.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acids / pharmacology
  • Amino Acid Sequence
  • Bacterial Proteins / genetics
  • Drug Resistance
  • Duodenal Ulcer / genetics*
  • Duodenal Ulcer / metabolism
  • Duodenal Ulcer / pathology
  • Female
  • Gene Frequency
  • Genes, Bacterial*
  • Helicobacter pylori / drug effects
  • Helicobacter pylori / genetics*
  • Helicobacter pylori / physiology
  • Humans
  • Hydrogen-Ion Concentration
  • Interleukin-8 / biosynthesis
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Signal Transduction / genetics
  • Virulence Factors / genetics


  • Acids
  • Bacterial Proteins
  • DupA protein, Helicobacter pylori
  • Interleukin-8
  • Virulence Factors