Conservation of the cytotoxin-associated (cag A) gene of Helicobacter pylori and investigation of association with vacuolating-cytotoxin activity and gastroduodenal disease

Abstract Polymerase chain reaction (PCR) amplification and DNA hybridization analyses were used to test for the presence of the cytotoxin-associated ( cag A) gene in 108 strains of Helicobacter pylori . Fifty-two geographically diverse strains of known vacuolating cytotoxin activity, and 56 recent UK clinical isolates from patients with duodenal ulceration ( n =28) and from healthy individuals who were endoscopically normal ( n =28) were studied. Overall, cag A was detected by PCR in 74 (69%) strains and DNA hybridization provided evidence of gene homologues in a further eight strains. For 96% of the cytotoxin-producing strains and 46% of the non-cytotoxin producing strains, there was a close association either with presence or absence of cag A. At the genomic level, Southern blot DNA hybridization showed that cag A was probably present in a single copy in most of the H. pylori tested, and that Hae III restriction site variation within and around the gene provided additional markers of diversity for the species. As 40% of the cag A containing strains did notnproduce an active cytotoxin, and no significant association between cag A presence and DU-disease was observed, we concluded that the presence of the cag A gene in H. pylori could not be used as a single reliable predictor of higher risk patients.