Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori

Background & Aims: vacA encodes the vacuolating cytotoxin of Helicobacter pylori and exhibits marked variation in signal sequence and midgene coding regions, The implications for gastroduodenal pathology are unknown, The aim of this study was to define the association of vacA genotype with gastric inflammation and injury, in vitro cytotoxin activity, and peptic ulceration, Methods: Sixty-one consecutive dyspeptic patients underwent endoscopy and gastric biopsy, The biopsy specimens were processed for H. pylori culture, and 52 specimens were also processed for histology, H. pylori vacA was typed by polymerase chain reaction and colony hybridization. Cytotoxin activity was assessed by a HeLa cell vacuolation assay. Results: vacA signal sequence type sla strains were associated with greater antral mucosal neutrophil and lymphocyte infiltration than s1b or s2 strains (P < 0.05). vacA midregion type mi strains were associated with greater gastric epithelial damage than m2 strains (P < 0.05), Both midregion and signal sequence were associated with cytotoxin activity in vitro, Duodenal ulcer disease occurred in 89% of 18 patients with s1a strains vs. 29% of 14 with s1b strains (P < 0.01), 20% of 10 with s2 strains (P < 0.001), and 16% of 19 uninfected patients (P < 0.001). Conclusions: H. pylori strains of vacA signal sequence type sla are associated with enhanced gastric inflammation and duodenal ulceration. vacA s2 strains are associated with less inflammation and lower ulcer prevalence.