Conservation of the cag pathogenicity island is associated with vacA alleles and gastroduodenal disease in South African Helicobacter pylori isolates

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Abstract
BACKGROUND The development of clinically significant disease in South Africa is associated with the vacuolating cytotoxin gene (vacA) s1 genotype but not with the presence of the cytotoxin associated gene cagA. cagA occurs in >95% of South African isolates and is a variable marker for the entirecag pathogenicity island (PAI). AIM To characterise the cagPAI in South African isolates and to investigate if structural variants of this multigene locus were associated with variations in vacA status and clinical outcome. PATIENTS AND METHODS We studied 109Helicobacter pylori strains (36 from patients with peptic ulceration, 26 with gastric adenocarcinoma, and 47 with no pathology other than gastritis) for differences in selected genes of the cagPAI and alleles ofvacA by polymerase chain reaction. RESULTS All strains were cagA +. Sixty five (60%) strains had an intact contiguous cagPAI; 78% of peptic ulcer isolates, 73% of gastric adenocarcinoma isolates, but only 40% of gastritis alone isolates (p< 0.01). The entirecagII region was undetectable in 23% of gastritis alone isolates but in only 8% of peptic ulceration isolates (pvacA signal sequence and mid region demonstrated a strong relationship between the virulence associated vacA s1 (pvacA m1 (p=0.05) alleles and an intactcagPAI. CONCLUSION Although a complete cagPAI was a feature of most infected individuals, deletions in the 5′ region of this genetic locus were associated with gastritis alone and with the non-cytotoxic s2/m2vacA genotype.