Duodenal ulcer promoting gene of Helicobacter pylori.
OBJECTIVE
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.
Lu
Hong
H
Department of Medicine/Gastroenterology, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Hsu
Ping-I
PI
Graham
David Y
DY
Yamaoka
Yoshio
Y
D000143:Acids / Q000494:pharmacology; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics; D004351:Drug Resistance; D004381:Duodenal Ulcer / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016209:Interleukin-8 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D015398:Signal Transduction / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics
D000143:Acids; D001426:Bacterial Proteins; C528428:DupA protein, Helicobacter pylori; D016209:Interleukin-8; D037521:Virulence Factors