Heterogeneity in the Helicobacter pylori vacA and cagA genes: association with gastroduodenal disease in South Africa?

Abstract

Background-Helicobacter pylori infection is universally associated with gastritis, but only sometimes with clinically significant disease. Candidate virulence markers seem to be useful in identifying the pathogenic infections in some populations. Aims-To investigate the association between putative virulence markers and disease in an African population. Methods-Fifty nine H pylori strains isolated from dyspeptic patients (11 with peptic ulceration, eight with gastric adenocarcinoma, and 28 with no pathology other than gastritis) were studied for diVerences in the genes vacA and cagA. Results-Forty seven (80%) of 59 strains had the vacA signal sequence genotype s1 (one s1a, 46 s1b) and 12 (20%) had subtype s2. vacA mid-region analysis revealed that 40 (68%) strains were vacA m1 and 19 (32%) were m2. All 14 strains from patients with peptic ulceration were vacA s1, in contrast to 23 (66%) of 35 strains from patients with gastritis alone (p<0.01). vacA s2 was found exclusively in patients with gastritis alone (p<0.01). All strains isolated from patients with gastric adenocarcinoma were s1b/m1 (p<0.005 versus gastritis alone). cagA was detectable in 56 (95%) of 59 isolates. Strains from patients with peptic ulceration (12/13 versus 19/30 with gastritis alone, p=0.05) had the shortest fragment length in the 3' region of cagA, while 4/10 strains from patients with gastric cancer had the longest fragment length in this region (p<0.02 versus gastritis alone). Conclusion-In this study, the vacA s1 genotype, and fragment length of the 3' region of cagA identified isolates associated with significant clinical disease. The vacA s1bm1 genotype seems to be strongly associated with gastric cancer. (Gut 1999;45:499-502)

Prevalência da infecção por Helicobacter pylori e das lesões precusoras do câncer gástrico em pacientes dispéticos

“…Vários estudos têm demonstrado que a infecção com H. pylori cag-A positivo é associada a alterações no ciclo celular e apoptose do epitélio gástrico e com níveis mais acentuados de inflamação (23,31) . O H. pylori cag-A positivo também tem sido associado com maior intensidade de atrofia e MI (20,26,30) .…”

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

“…These results suggest that s1a/m1 strains have the most virulent allelic type activity, 77,80 while vacA s2 strains are rarely associated with ulcer disease and are uncommon in many populations. [80][81][82][83][84] The link between the ability of a strain to induce epithelial cell vacuolation in vitro and peptic ulcer disease in vivo seems to be consistent but not invariable. 77 Among strains from populations in the United States, the ability of vacA s1a strains to induce ulcer disease was higher than that of vacA s1b strains.…”

“…No vacA s1a strains were present, and 100% of patients with peptic ulceration harbored strains with vacA s1b allele. 84 The high prevalence of strains with vacA s1b genotype is not confined to South Africa; these strains are also widespread in Brazil and Portugal, where higher prevalence rates of peptic ulceration and gastric adenocarcinoma have been reported. 86,89 Additionally, in the South African population, the vacA s2 allele was found exclusively in the group of individuals without any pathology, consistent with observations that vacA s2 strains are minimally or non-ulcerogenic.…”

“…86,89 Additionally, in the South African population, the vacA s2 allele was found exclusively in the group of individuals without any pathology, consistent with observations that vacA s2 strains are minimally or non-ulcerogenic. [80][81][82][83][84] On the other hand, recent studies of a worldwide collection of strains indicate that subtype s1c was observed exclusively in isolates from East Asia and appears to be the major s1 allele in that part of the world. Nevertheless, whether s1c strains are phenotypically different from s1a and s1b strains remains to be determined.…”

Helicobacter pylori persistence: biology and disease

“…pylori-induced gastric carcinogenesis is more likely when the interaction between H. pylori and the host is more interactive; inflammation is more intense and the effects on epithelial cells are more damaging (S106). This may reflect colonization by more interactive H. pylori strains: cag + strains induce more inflammation and cell cycle effects (4), and vacA s1/m1 strains cause more direct epithelial damage (27,58,59, S105). Host cytokine polymorphisms enhance the inflammatory response (83, 84, S14, S75).…”