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Approximately 50% of Helicobacter pylori strains produce a cytotoxin that is encoded by vacA and that induces vacuolation of eukaryotic cells. Mosaicism in vacA alleles was reported, and there are three different families of vacA signal sequences (s1a, s1b, and s2) and two different families of middle-region alleles (m1 and m2). In addition, the vacA genotype of a strain is associated with its cytotoxin phenotype and its capacity to induce peptic ulceration. To clarify the strain diversity of H. pylori in Japan, 87 Japanese clinical isolates of H. pylori (40 from patients with chronic atrophic gastritis, 25 from patients with duodenal ulcer, 16 from patients with gastric ulcer, 3 from patients with both duodenal and gastric ulcers, and 3 from patients with intestinal type gastric cancer) were characterized by vacA typing by PCR and DNA sequencing. Eighty-four of the 87 isolates were s1a/m1, one was s1b/m1, and two could not be typed. Moreover, all isolates in this study were cagA positive. There were no distinct differences between the cytotoxin-producing strains and cytotoxin-nonproducing strains within the 0.73-kb middle region. Japanese strains were highly homologous, with more than 96% identity in this region, in which maximum divergence has been reported. In addition, there were no associations between the specific vacA types and the level of in vitro cytotoxin activity or the clinical consequences. These results indicate that the cagA-positive, s1a/m1-type strains are common in Japan, regardless of the vacA phenotype or clinical outcome.

RESULTS. Of 70 -90% of patients with gastric adenocarcinoma. The epidemiologic features of gastric adenocarcinoma and H. pylori infection are similar,

Some clinical isolates of Helicobacter pylori fail to express vacuolating cytotoxin, despite possessing a copy of the vacA gene on the chromosome. To gain insight into the differences between vacA from cytotoxic and noncytotoxic strains, the vacA open-reading frames from 16 cytotoxic and 22 noncytotoxic strains were sequenced. Mutations that cause truncation of VacA in 11 of 22 noncytotoxic strains were identified, including internal duplication, large deletion, 1-bp insertion, and non-sense mutations. In contrast, none of the 16 cytotoxic strains had any truncation of VacA. Four cytotoxic strains had inserted sequences downstream of vacA. Three were mini-IS605, and the other was a putative rfaJ gene that encodes lipopolysaccharide glucosyltransferase. The rfaJ gene identified in this study had a poly(C) tract, resulting in premature termination of the gene product. The phylogenetic tree based on the vacA open-reading frame indicated that two different H. pylori lineages are circulating in Japan and the West.

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