Association of Helicobacter pylori genotype with gastroesophageal reflux disease and other upper gastrointestinal diseases

Am J Gastroenterol. 2000 Mar;95(3):659-69. doi: 10.1111/j.1572-0241.2000.01970.x.


Objective: Helicobacter pylori (H. pylori) is a recognized pathogen, but it may also have a protective effect for gastroesophageal reflux disease (GERD). We compared the prevalence of potential virulence factors (cagA, cagE, vacA genotypes) in GERD to other upper gastrointestinal diseases and controls.

Methods: A total of 405 patients underwent gastroscopy with H. pylori isolation and serum testing. Patient diagnostic subgroups were prospectively defined. Genotypes were determined by amplification using polymerase chain reaction. CagA antibodies were determined by western blot, enzyme-linked immunosorbent, and flow microsphere immunofluorescent assays.

Results: Patients were grouped as follows: nonulcer dyspepsia (26%), GERD (20%), gastric ulcer (17%), duodenal ulcer (12%), gastric cancer (6%), or controls (19%). The cagA gene was present in 94-97% of subjects in all categories, but the cagA antibody was less prevalent in nonulcer dyspepsia (69%, 95% CI: 48-86%, p = 0.02) and GERD (69%, CI: 39-91%, p < 0.05) than in those with gastroduodenal pathology including gastric ulcer, duodenal ulcer, and gastric cancer (92%, CI: 81-98%). The cagE gene and vacA S1 genotype were more frequent in patients with gastroduodenal pathology (p < 0.01). GERD was associated with a significantly lower rate of vacA S1 genotype than controls (29% (CI: 10-56%) versus 80% (CI: 59-93%), p < 0.01). The vacA S1 genotype was associated with the presence of cagA antibodies.

Conclusions: The cagE and vacA S1 genotypes are more prevalent in patients with peptic ulcer or gastric cancer, suggesting a potential function in virulence for these genes. However, the vacA S1 genotype was also more prevalent in controls than GERD, suggesting a potential protective effect against GERD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Bacterial*
  • Bacterial Proteins / genetics
  • Dyspepsia / microbiology*
  • Gastroesophageal Reflux / microbiology*
  • Gastroscopy
  • Gene Expression Regulation, Bacterial / physiology
  • Genotype*
  • Helicobacter Infections / microbiology*
  • Helicobacter pylori / genetics*
  • Humans
  • Peptic Ulcer / microbiology*
  • Polymerase Chain Reaction
  • Stomach Neoplasms / microbiology*


  • Antigens, Bacterial
  • Bacterial Proteins
  • VacA protein, Helicobacter pylori
  • cagA protein, Helicobacter pylori