CLINICAL AND PATHOLOGICAL IMPORTANCE OF HETEROGENEITY IN VACA, THE VACUOLATING CYTOTOXIN GENE OF HELICOBACTER-PYLORI

Background & Aims: vacA encodes the vacuolating cytotoxin of Helicobac ter pylori and exhibits marked variation in signal sequence and midgen e coding regions, The implications for gastroduodenal pathology are un known, The aim of this study was to define the association of vacA gen otype with gastric inflammation and injury, in vitro cytotoxin activit y, and peptic ulceration, Methods: Sixty-one consecutive dyspeptic pat ients underwent endoscopy and gastric biopsy, The biopsy specimens wer e processed for H. pylori culture, and 52 specimens were also processe d for histology, H. pylori vacA was typed by polymerase chain reaction and colony hybridization. Cytotoxin activity was assessed by a HeLa c ell 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 m 2 strains (P < 0.05), Both midregion and signal sequence were associat ed with cytotoxin activity in vitro, Duodenal ulcer disease occurred i n 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 uninfe cted patients (P < 0.001). Conclusions: H. pylori strains of vacA sign al sequence type sla are associated with enhanced gastric inflammation and duodenal ulceration. vacA s2 strains are associated with less inf lammation and lower ulcer prevalence.