Clinical Relevance and Sequence Analysis of the Helicobacter pylori dupA Region from Two Areas in Japan with Different Gastric Cancer Risks

Aims: We investigated the virulence and sequences of duodenal ulcer-promoting gene A (dupA) of Helicobacter pylori (H. pylori) isolated from 2 areas in Japan with different gastric cancer risks. Methods: The dupA status of 248 Japanese H. pylori strains (111 from Fukui and 137 from Okinawa) isolated from patients with duodenal ulcers, gastric ulcers, chronic gastritis, or gastric cancer was evaluated by dot-blot hybridization followed by polymerase chain reaction. Sequence analyses of dupA and its upstream region were performed in 15 strains. Results: In both areas, no significant association was observed between dupA and the evaluated clinical outcomes. In a multivariable logistic regression, dupA positivity was independently associated with strains isolated from Okinawa, showing the lowest incidence of gastric cancer in Japan, and with East Asian-type cagA positivity (odds ratio (OR)=2.128, 95% confidence interval (CI) =1.146-3.949 and OR=12.924, 95% CI=1.689-98.901, respectively). Sequence alignment showed dupA was divided into 2 genotypes: a Shi470-type (2499 bp) and a J99-type (1839 bp). Among 60 dupA + Japanese strains, 58 (96.7%) were of the Shi470-type and 2 of the J99-type. The nucleotide sequences of 13 Shi470-type Japanese isolates from both areas were highly homologous (98.9%) to each other and a remote Amazonian strain, Shi470. Of these, 12 (92.3%) carried intact full-length dupA. Conclusion: In Japan, dupA appeared to be associated with East Asian-type cagA and with host residence in Okinawa. The intact genotype of the Shi470-type dupA was the major form in Japan. Immunogastroenterology 2012; 1:127-135