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

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 entire cag 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 109 Helicobacter 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 of vacA 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 entire cagII region was undetectable in 23% of gastritis alone isolates but in only 8% of peptic ulceration isolates (p<0.05). The vacA signal sequence and mid region demonstrated a strong relationship between the virulence associated vacA s1 (p<0.005) and vacA m1 (p=0.05) alleles and an intact cagPAI. 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/m2 vacA genotype.