Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori.
OBJECTIVE
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 s1a strains were associated with greater antral mucosal neutrophil and lymphocyte infiltration than s1b or s2 strains (P < 0.05). vacA midregion type m1 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 s1a are associated with enhanced gastric inflammation and duodenal ulceration. vacA s2 strains are associated with less inflammation and lower ulcer prevalence.
Atherton
J C
JC
Division of Gastroenterology, University Hospital, Nottingham, England.
Peek
R M
RM
Tham
K T
KT
Cover
T L
TL
Blaser
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001241:Aspirin / Q000008:administration & dosage; D001284:Atrophy; D001426:Bacterial Proteins / Q000235:genetics*; D003603:Cytotoxins / Q000235:genetics*; D004381:Duodenal Ulcer / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D005753:Gastric Mucosa / Q000473:pathology; D005798:Genes, Bacterial / Q000235:genetics*; D005838:Genotype; D016480:Helicobacter pylori / Q000235:genetics*; D006801:Humans; D007111:Immunity, Cellular; D008214:Lymphocytes; D008875:Middle Aged; D009504:Neutrophils; D011446:Prospective Studies; D013276:Stomach Ulcer / Q000276:immunology / Q000382:microbiology* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001426:Bacterial Proteins; D003603:Cytotoxins; C074689:VacA protein, Helicobacter pylori; D001241:Aspirin