Helicobacter pylori cag pathogenicity island genes: clinical relevance for peptic ulcer disease development in Brazil

Abstract

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...

High prevalence of duodenal ulcer in a tertiary care hospital in the city of São Paulo, SP, Brazil

“…Prevalence of peptic ulcer in Brazil has been poorly studied in spite of the high prevalence of H. pylori infection. A report from the South part of Brazil found low prevalence of duodenal (24) , being more frequent in the male gender (15,24) , despite the preponderance of women in the peptic ulcer group in our studied population (14) .…”

“…However, infection with more pathogenic H. pylori isolates with positive cagPAI genes (15,17) was previously shown as risk of ulcer disease outcome. Other factors were being between 40 and 60 years of age, being male, cigarette smoking, alcohol consumption, use of aspirin or NSAIDs, heavy social psychological stress, frequent mobility, irregular working hours, low socioeconomic status, higher acid output, and heredity (4,5,29) .…”

“…Within the peptic ulcer group, gastric ulcer group had significantly higher age; the incidence of gastric ulcer has been relatively higher in the elderly people, compared to that of duodenal ulcers (26) that may be due to lower defensive factors such as poor gastrin-elevating action capable of healing by its trophic effect (8) , decreased mucus, bicarbonate secretion and prostaglandins (12) . Endoscopic erosive antral gastritis was more frequent than corpus gastritis in both gastric and duodenal ulcer groups, in our previous report the activity of inflammation was also more intense in the antrum of peptic ulcer patients (14) ; in addition, gastritis was more intense in the peptic ulcer group than in those with normal endoscopy and H. pylori positive (15) . Endoscopic diagnosis has been 62% as sensitive as histological diagnosis for erosive gastritis and 84% for atrophic gastritis in the antrum (10) .…”

Prevalence, diversity and disease association of Helicobacter pylori in dyspeptic patients from Pakistan

“…pylori carries various virulence factors, such as vacuolating cytotoxin A (VacA), CagA cytotoxin and sialic acid binding adhesin (SabA), that are implicated in the development of pathological conditions of gastric mucosa [9]. CagA is encoded by the cytotoxin associated gene A (cagA) present in the Cag pathogenicity island [10,11]. H. pylori strains can be grouped as Western and East Asian subtypes on the basis of polymorphism in the 3′ repeat region of the cagA gene [12].…”

Validation of a rapid stool antigen test for diagnosis of Helicobacter pylori infection

“…Helicobacter pylori (H. pylori), spiral or curved gram-negative microaerophilic, flagellate bacilli has been considered the etiological cause of gastritis, peptic ulcer disease 21,24 and associated with the development of gastric cancer 25 .…”