Gastroenterology

Gastroenterology

Volume 128, Issue 4, April 2005, Pages 833-848
Gastroenterology

Clinical-alimentary tract
Duodenal ulcer promoting gene of Helicobacter pylori

https://doi.org/10.1053/j.gastro.2005.01.009Get rights and content

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.

Section snippets

H pylori studied

For the study of the possible relation between vir homologues and clinical outcome in H pylori infection, we examined a large number of H pylori from different geographic regions to reduce the likelihood of spurious associations based on examining small numbers or restricted regional circulation of a particular genotype. We examined H pylori obtained from patients in East Asia (Kyoto Prefectural University of Medicine, Kyoto, Japan, and Guro Hospital, Korea University College of Medicine,

Prevalence of the vir homologue genes and clinical outcomes

We examined 500 H pylori isolates for the 14 known vir homologue genes previously detected within the H pylori genome. Specimens were obtained from 294 men and 206 women with a mean age of 52.4 years. There were 160 subjects from Japan (presentations included 50 gastritis, 30 DU, 50 GU, and 30 gastric cancer), 175 from Korea (presentations included 30 gastritis, 65 DU, 30 GU, and 50 gastric cancer), and 165 from Colombia (presentations included 40 gastritis, 45 DU, 30 GU, and 50 gastric cancer).

Discussion

Although a number of putative virulence factors of H pylori had been reported (eg, the cag PAI, vacA, babA, and oipA), their presence has typically been associated with an increased risk of both gastric cancer and peptic ulcers. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 We report an H pylori gene (jhp0917-0918: dupA) whose presence was related to increased risk of DU and with neutrophil infiltration as well as protection against atrophy, intestinal metaplasia, and gastric cancer. This pattern mirrors the

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    Supported in part by the Office of Research and Development Medical Research Service Department of Veterans Affairs (to D.Y.G.), by National Institutes of Health grants R01 DK62813 (to Y.Y.), and by Public Health Service grant DK56338, which funds the Texas Gulf Coast Digestive Diseases Center.

    1

    P-I.H.’s present address is Division of Gastroenterology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.

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