The purpose of this study was to verify whether the presence of any of the Helicobacter pylori cagPAI genes or segments -cagA, cagA promoter, cagE, cagM, tnpB, tnpA, cagT and the left end of the cag II (LEC) region -would be a useful marker for the risk of peptic ulcer disease development. H. pylori DNA extracted from positive urease tests of 150 peptic ulcer patients and 65 dyspeptic controls was analysed by PCR. Duodenal ulcers were present in 110, gastric ulcers in 23 and both gastric and duodenal ulcers in 17 patients. A significant association (P <0.001) was found between a conserved cagPAI and peptic ulcer disease (34 %). The positivity of the cagA gene varied according to the region of the gene that was amplified. The region near to the promoter was present in almost all of the H. pylori isolates (97.2 %). The segment from nt 1764 to 2083 and the extreme right end were frequently deleted in the isolates from the controls (P <0.01). The positivity of the promoter region of cagA and cagT, cagE, cagM and LEC showed a significant difference between the isolates from peptic ulcer patients and from the controls (P <0.01). Patients usually had moderate gastritis; however, the intensity of the active inflammation was higher in the peptic ulcer group (P <0.001). cagT, cagM, LEC and the right end terminus of the cagA-positive H. pylori isolates were associated with a 27-fold, 8-fold, 4-fold and 4-fold risk of peptic ulcer disease, respectively, and may be useful markers to identify individuals at higher risk of peptic ulcer disease development in Brazil.
INTRODUCTIONHelicobacter pylori colonizes the human stomach causing chronic gastritis. A small number of individuals progress to peptic ulcer or gastric cancer. Multiple bacterial and/or host factors are involved in disease development (Backert et al., 2004;Peek, 2005).H. pylori clinical isolates are classified into two types according to their degree of pathogenicity. Type I, associated with severe disease pathology, expresses functional VacA (vacuolating cytotoxin A) and contains an insertion of 40 kb of foreign DNA, the cag (cytotoxin-associated gene) pathogenicity island (cagPAI). Type II lacks cagPAI, harbours a non-toxic form of VacA and is regarded as less virulent (Censini et al., 1996;Backert et al., 2004).The cagPAI may be divided into two regions, cag I and cag II, by a novel insertion sequence (IS605). There are approximately 16 and 15 open reading frames in cag I and cag II, respectively (Censini et al., 1996; Akopyants et al., 1998). The cagPAI encodes a type IV secretion system, which delivers CagA into the cytosol of gastric epithelial cells (Covacci & Rappuoli, 2000) through a rigid needle structure covered by Cag7 or CagY, a VirB10-homologous protein, and CagT, a VirB7-homologous protein, at the base (Rohde et al., 2003). CagA is tyrosine-phosphorylated by Src-family kinases (Selbach et al., 2002), triggering the elongated hummingbird phenotype (Higashi et al., 2005) similar to that of hepatocyte growth factor (Segal et al., 1999). Numerous phosp...