Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin - PubMed (original) (raw)

Clinical relevance of the Helicobacter pylori gene for blood-group antigen-binding adhesin

M Gerhard et al. Proc Natl Acad Sci U S A. 1999.

Abstract

Infection with Helicobacter pylori is associated with different human gastric diseases. Biochemical studies, in vitro adherence assays, and in vivo animal models revealed that epithelial attachment of H. pylori can be mediated by the blood-group antigen-binding adhesin (BabA) targeting human Lewis(b) surface epitopes. Studies with transgenic mice expressing the Lewis(b) epitope have shown that such attachment can alter disease outcome. In the current study, the presence of the babA2 gene encoding the adhesin was investigated in clinical isolates from a German population by using PCR and reverse transcription-PCR. A positive genotype was correlated to allelic variations in the genes encoding VacA and CagA and also to the prevalence of duodenal ulcer, distal gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and antral gastritis. The presence of babA2 was significantly associated with duodenal ulcer (P = 0.0002) and adenocarcinoma (P = 0.033). In contrast, type 1 strains (vacAs1- and cagA-positive) were associated with only duodenal ulcer (P = 0.004) but not adenocarcinoma (P = 0.235). Genotype presence of babA2, vacAs1, and cagA ("triple-positive" strains) showed a highly significant correlation to the prevalence of ulcer (P = 0.000002) and adenocarcinoma (P = 0.014) and discriminated significantly better between disease outcome than did the current type 1 classification. These results indicate that the babA2 gene is of high clinical relevance and would be a useful marker to identify patients who are at higher risk for specific H. pylori-related diseases.

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Figures

Figure 1

Figure 1

BabA gene organization, nucleotide sequence (adapted from ref. 28), and primer positions for mismatch PCR. The binding of the sense primer to babA1 and babA2 genes is shown in relation to repeat motif. Matches are indicated by vertical bars; mismatches are indicated by asterisks. Regions of high homology to other genes (OMP9) are indicated by gray shading of open bars.

Figure 2

Figure 2

Schematic illustration of the distribution of vacAs1, cagA, and babA2 strains in a total of 35 H. pylori isolates from patients with gastritis.

Figure 3

Figure 3

babA2, type 1, and triple-positive genotypes in H. pylori isolates from patients with different diseases. GC, gastric adenocarcinoma; UD, duodenal ulcer.

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