IDENTIFICATION AND ANALYSIS OF A NEW VACA GENOTYPE VARIANT OF HELICOBACTER-PYLORI IN DIFFERENT PATIENT GROUPS IN GERMANY

The vacuolating cytotoxin of Helicobacter pylori (VacA) is known to ca use cell damage to mammalian cells and is suspected to give rise to ga stric epithelial lesions that might lead to peptic ulcer disease. As s hown recently, the gene encoding VacA exhibits genetic variation, with three different families of signal sequences (s1a, s1b, and s2) and t wo families of midregion sequences (m1 and m2). In order to investigat e the relationship between the presence of specific vacA genotypes and peptic ulceration, the vacA genotypes of 158 clinical isolates of H. pylori were determined. The study group consisted of 106 patients with duodenal ulceration; 52 patients with nonulcer dyspepsia (NUD) were u sed as controls. H. pylori of genotype s1 was isolated from 96% of the patients with ulcerations, whereas genotype s2 was only present in 4% , indicating a strong correlation between the vacA genotype and peptic ulceration (P < 0.001). In contrast, 31% of the patients from the NUD control group were infected with strains of vacA genotype s2. Particu lar midregion genotypes (m1 and m2) were not associated with clinical manifestations. The midregions from 18% of the isolates could not be c lassified by the proposed scheme. DNA sequencing revealed high homolog y between the untypeable midregions and that of genotype m1, with mult iple base pair exchanges, some affecting the primer annealing site. Co mpared to those of m1 and m2 alleles, the divergent midregions from un typeable strains showed clustering, indicating the presence of a furth er subfamily of sequences in the midregion of vacA in German isolates, for which we propose the term ''m1a.'' A new specific primer that we designed for typing m1a isolates might be useful in other studies.