dupA polymorphisms and risk of Helicobacter pylori-associated diseases.

The dupA of Helicobacter pylori has been suggested as a virulence marker associated with the development of duodenal ulcer disease. However, the studies performed in different geographical areas have shown that there are variations in the prevalence of dupA and its association with H. pylori clinical outcomes. Our group did not observe associations between the presence of dupA and H. pylori clinical outcomes in Brazil. On the other hand, we observed 2 mutations in the sequence of dupA that lead to stop codons: a deletion of an adenine at position 1311 and an insertion of an adenine at position 1426 of the gene. Our aim was to evaluate associations of the presence of dupA with duodenal ulcer and gastric cancer, considering dupA-positive only those H. pylori strains that do not have the mutations in the gene sequence. We also evaluated the effect of infection with a strain carrying an intact dupA on the gastric mucosa histology and IL-8 gastric levels. Colonization with strains that had the intact dupA was negatively associated with gastric carcinoma (p=0.001, OR=0.32, 95% CI=0.16-0.66). The presence of dupA was also associated with an increased degree of antral mucosa inflammation (p=0.01) and with decreased corpus atrophy (p<0.01) as well as with increased gastric mucosa IL-8 levels (p=0.04). In conclusion, the infection with a H. pylori strain containing the dupA without the stop codon polymorphisms is associated with a lower risk of development of gastric carcinoma in Brazilian subjects.

Lack of association between Helicobacter pylori infection with dupA-positive strains and gastroduodenal diseases in Brazilian patients.

Duodenal ulcer-promoting gene (dupA) was recently described as a new putative Helicobacter pylori virulence marker associated with an increased risk for duodenal ulcer and reduced risk for gastric carcinoma in Japan and Korea. Since differences regarding the association among H. pylori markers and H. pylori-associated diseases have been demonstrated around the world, we evaluated the presence of the gene in 482 strains from Brazilian children (34 with duodenal ulcer and 97 with gastritis) and adults (126 with duodenal ulcer, 144 with gastritis and 81 with gastric carcinoma) by PCR using the described primers and an additional set of primers based on Brazilian strain sequences. The results were confirmed by sequencing. The presence of cagA was investigated by PCR and also included in the analysis. dupA was present in 445 (92.32%) and absent in 29 (6.02%) strains. All samples from children with and without duodenal ulcer were dupA-positive (p=1.0). No association was observed among the strains from adults with gastritis (92.36%), duodenal ulcer (87.30%, p=0.30) and gastric carcinoma (87.65%, p=0.31). Conversely, cagA-positve status remained independently associated with duodenal ulcer (children: odds ratios (OR)=5.58, 95% confidence intervals (CI)=1.67-18.50; adults: OR=3.33, 95% CI=2.14-5.19) and gastric carcinoma (OR=6.58, 95% CI=3.51-12.30) in multivariate analyses. The presence of dupA was significantly higher in strains from children than in those from adults (p=0.01). In conclusion, dupA is highly frequent and not associated with H. pylori-associated diseases in both Brazilian adults and children, which points to regional differences in the distribution of the gene.

Gastric epithelial cell proliferation and cagA status in Helicobacter pylori gastritis at different gastric sites.

OBJECTIVE: Helicobacter pylori infection causes hyperproliferation which is believed to predispose to the development of gastric carcinoma. The aim of this study was to analyze epithelial cell proliferation topographically in H. pylori gastritis in relationship to cagA status. MATERIAL AND METHODS: The proliferative index (PI: Ki-67-labeled nuclei/total number of foveolar nuclei) was determined in gastric mucosa biopsies taken at the antrum (lesser and greater curvatures), incisura, and corpus (greater curvature) from 78 patients with H. pylori gastritis and 20 H. pylori-negative patients. H. pylori and cagA status were determined by polymerase chain reaction (PCR) and serology. RESULTS: PIs were significantly higher in H. pylori- and cagA-positive patients, in comparison with H. pylori- and cagA-negative patients, at all sites (p

Distribution of vacA genotypes in Helicobacter pylori strains isolated from Brazilian adult patients with gastritis, duodenal ulcer or gastric carcinoma.

This PCR-based analysis is the first molecular epidemiological study in Brazil testing Helicobacter pylori cagA and vacA distribution in adults with gastric complaints, that includes a large number of carcinoma patients. Multiple-strain infection was identified in 11/13.4% patients. vacA s1-m1 and cagA(+) genotypes were the most common in patients with a non-mixed infection. All vacA s1 strains were s1b, so subtyping s1 strains was not useful. vacA s1b-m1 and cagA(+) strains were associated with higher prevalence of peptic ulcer and gastric carcinoma than vacA s2-m2 and cagA(-) ones. In conclusion, cagA and vacA genotyping may have clinical relevance in Brazil.

Gastrite associada ao Heliocobacter pylori em adultos e crianças: estudo comparativo / Helicobacter pylori associated gastritis in adults and children: a comparative study

A reaçäo inflamatória da gastrite por H. pylori é pouco estudada em crianças. Objetivos: Analisar a reaçäo inflamatória e imune da gastrite por H. pylori em adultos e crianças, 15 com ulcera duodenal (UD) e 47 adultos, 21 com UD. A análise histológica foi feita, segundo o Sistema Sydney; o exsudato imune foi semi-quantificado; o microrganismo foi pesquisado por cultura, urease e histologia. Os genes ureA e cagA foram pesquisados por Elisa. Resultados: Em crianças, a reaçäo inflamatória predominou nos casos com UD em relaçäo àqueles sem UD (p<0,01). Nos dois grupos, a inflamaçäo predominou no antro (p<0,01), mas a atividade foi semelhante no antro e corpo. A resposta imune foi idêntica no antro e no corpo dos casos com UD. Nos adultos com UD, a inflamaçäo e a atividade foram mais intensas no antro do que no corpo (P<0,0007). A reaçäo imune predominou no antro (p<0,032) em ambos os grupos. Näo houve correlaçäo entre a colonizaçäo bacteriana e a reaçäo inflamatória e imune. Nos casos com UD, isolaram-se predominantemente cepas cagA+, em crianças (93 por cento) e adultos (83 por cento). A infecçäo por cepas cagA+ correlacionou-se com o exsudato plasmocitário (p<0,03) e com a inflamaçäo e a atividade (p<0,04) em crianças. Conclusäo: A resposta inflamatória na gastrite associada ao H. pylori é diferente em adultos e crianças. Conclusäo A resposta inflamatória na gastrite associada ao H. pylori é diferente em adultos e crianças. Conclusäo, o que pode estar relacionado com diferenças na secreçäo ácida e com aspectos evolutivos da infecçäo

Serological and direct diagnosis of Helicobacter pylori in gastric carcinoma: a case-control study.

This study evaluated the sensitivity of serological and direct methods for the diagnosis of Helicobacter pylori infection in 127 patients with gastric carcinoma and in 127 controls without this disease, matched for age and sex. Antral and oxyntic mucosal specimens were obtained from all patients, at operation in patients with gastric carcinoma and at endoscopy from controls. The urease test, microscopy of stained smears and culture for H. pylori were performed on all specimens. Sera from all patients were tested for antibodies to H. pylori by a highly sensitive and specific IgG-ELISA. Culture, urease test, stained smear and ELISA were significantly less sensitive in the patients with gastric carcinoma than in control subjects. However, the combination of several methods improved the diagnosis of H. pylori infection in the gastric carcinoma group. Infection was significantly more frequent in the gastric carcinoma patients than in the controls. H. pylori infection was associated with an increased risk of developing gastric carcinoma.