CONSERVATION OF THE CYTOTOXIN-ASSOCIATED (CAGA) GENE OF HELICOBACTER-PYLORI AND INVESTIGATION OF ASSOCIATION WITH VACUOLATING-CYTOTOXIN ACTIVITY AND GASTRODUODENAL DISEASE

Polymerase chain reaction (PCR) amplification and DNA hybridization analyses were used to test for the presence of the cytotoxin-associated (cagA) 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, cagA was detected by PCR in 74 (69%) strains and DNA hybridization provided evidence of gene homologues in a further eight strains. For 95% of the cytotoxin-producing strains and 46% of the non-cytotoxin producing strains, there was a close association either with presence or absence of cagA. At the genomic level, Southern blot DNA hybridization showed that cagA was probably present in a single copy in most of the H pylori tested, and that HaeIII restriction site variation within and around the gene provided additional markers of diversity for the species. As 40% of the cagA containing strains did not produce an active cytotoxin, and no significant association between cagA presence and DU-disease was observed, we concluded that the presence of the cagA gene in H. pylori could not be used as a single reliable predictor of higher risk patients.