Disease relevance of cagA

• Chronic infection with cagA-positive Helicobacter pylori is associated with the development of atrophic gastritis, peptic ulcers, and gastric adenocarcinoma [1].
• Furthermore, H. pylori strains carrying the cagA gene are more virulent than cagA-negative strains and are associated with the development of gastric adenocarcinoma [2].
• Transformed colonies were merged in soft-agarose medium after immortalized gastric epithelial cells were transfected with recombinant pLHCX retrovirus with cagA and/or dimethylhydrazine [3].
• Functional variability of cagA gene in Japanese isolates of Helicobacter pylori [4].
• The aim of this study is to analyze the genetic and functional variability of cagA gene of clinical strains in relation to gastric diseases [4].

High impact information on cagA

• METHODS: Genotypic variations in virulence-associated genes of H. pylori vacA (s and m regions) and cagA were determined in 221 subjects with chronic gastritis and 222 patients with gastric carcinoma by polymerase chain reaction (PCR)-line probe assay [5].
• Re: Helicobacter pylori and atrophic gastritis: importance of the cagA status [6].
• One of the initially atrophy-negative, cagA-positive subjects developed early gastric cancer [7].
• H. pylori strains can differ with respect to the presence of cagA (cytotoxin-associated gene A), a gene encoding a high-molecular-weight immunodominant antigen [7].
• In six of these 16 subjects (five cagA positive versus one cagA negative), atrophic gastritis was accompanied by the development of intestinal metaplasia (i.e., a change in the type of specialized cells present) (P = .02; Fisher's exact test; RR = 9.06; 95% CI = 1.16-71.0) [7].

Chemical compound and disease context of cagA

• The aim was to investigate the effect of cagA+ strains on PGE2 and enhance the understanding of the mechanisms leading to gastric diseases [8].
• Identification of cagA tyrosine phosphorylation DNA motifs in Helicobacter pylori isolates from peptic ulcer patients by novel PCR-restriction fragment length polymorphism and real-time fluorescence PCR assays [9].
• Evaluation of clarithromycin resistance and cagA and vacA genotyping of Helicobacter pylori strains from the west of Ireland using line probe assays [10].
• Intestinal metaplasia (IM) was categorised (type I, complete IM; types II and III, incomplete IM) by the high iron diamine stain; cagA status was ascertained by genotyping [11].
• Analysis of the 3' Variable Region of the cagA Gene of Helicobacter pylori Isolated in Koreans [12].

Biological context of cagA

• The cagA gene product CagA is injected into gastric epithelial cells, where it undergoes tyrosine phosphorylation by Src family kinases [1].
• The vacA s1a genotype was detected in 66.7, 96.4, and 87.9% of isolates from patients with NUD, DU, and GC, respectively, and its presence was significantly associated with that of DU (p = .004), GC (p = .043), and cagA gene (p = .021) [13].
• The coccoid H pylori contain completed cagA gene, which may be related to pathogenicity of them [14].
• CONCLUSION: The recombinant plasmid containing cagA gene from coccoid H pylori has been constructed successfully [14].
• RESULTS: cagA gene of 3,444 bp was obtained from the coccoid H pylori genome DNA [14].

Anatomical context of cagA

• The aim of this study was to investigate the relationship between cagA gene and cytokine messenger RNA (mRNA) expression in gastric mucosa [15].
• Active duodenitis was present only in patients with DU infected by cagA positive strains in the duodenum [16].
• RESULTS: B128-infected gerbils harbored high numbers of bacteria in the gastric antrum and corpus, whereas B128delta cagY and B128delta cagA colonized the antrum more densely than the corpus [17].
• Gastric cancer at the cardia is not associated with H. pylori infection or cagA -positive strains of H. pylori [18].
• The cagA gene product CagA is delivered into gastric epithelial cells where it localizes to the plasma membrane and undergoes tyrosine phosphorylation at the EPIYA-repeat region, which contains the EPIYA-A segment, EPIYA-B segment, and Western CagA-specific EPIYA-C or East Asian CagA-specific EPIYA-D segment [19].

Associations of cagA with chemical compounds

• In patients without atrophy, those infected with cagA+ had significantly higher (P = 0.03) PGE2 levels (53 +/- 1.1) than HP- patients (22.6 +/- 1.1) and greater levels (P = 0.29) than cagA- patients (35 +/- 1.3) [8].
• Although there was no significant association between 23S rDNA mutations and the vacA and cagA status, clarithromycin-susceptible strains more often contained mixed vacA genotypes, indicating the presence of multiple H. pylori strains [20].
• Southern hybridization of kanamycin-resistant H. pylori transformants demonstrated that the wild-type cagA gene had been disrupted by insertion of the kanamycin cassette, and immunoblot analysis showed that the mutant strains no longer produced the 128-kDa CagA protein [21].
• Expression of XylE after growth in broth culture revealed that basal levels of expression of cagA and urea in H. pylori were substantially greater than for picB [22].
• The cagA-negative H. pylori strains showed cytotoxin, urease, and phospholipase C activities, C3 binding and adherence similar to those of the isogenic wild-type strains [21].

Other interactions of cagA

• The presence of vacA alleles, cagA, cagE, iceA, and babA2 genotypes were determined by polymerase chain reaction (PCR) [13].
• Therefore, the aim of this study was to investigate the status of H. pylori strains regarding the babA and iceA alleles, as well as the cagA genotype, to reveal any association between these genotypes and clinical outcomes in Brazilian patients [23].
• The number of nonsynonymous substitutions was much higher in cagA than in glmM, indicating positive selection [24].
• Translocation of CagA was dependent on functional cagA gene and virulence (vir) genes of a type IV secretion apparatus composed of virB4, virB7, virB10, virB11 and virD4 encoded in the cag PAI of H. pylori [25].
• Included in the list of regulated factors were the known virulence genes cagA, vacA, and napA [26].

Analytical, diagnostic and therapeutic context of cagA

• Western blot revealed that cagA became phosphorylated in tyrosine site and bound with SHP-2 after transient expression of cagA DNA in gastric epithelial cells [27].
• The cagA status of each individual was determined at the follow-up visit with the use of an enzyme-linked immunosorbent assay designed to detect the presence of serum immunoglobulin G directed against the CagA protein [7].
• Each strain was characterized by random amplified polymorphic DNA (RAPD) fingerprinting. cagA was detected by polymerase chain reaction (PCR), Southern blotting, and colony hybridization [28].
• Meta-analysis of the relationship between cagA seropositivity and gastric cancer [18].
• To determine whether infection with a Helicobacter pylori strain possessing cagA is associated with an increased risk of development of adenocarcinoma of the stomach, we used a nested case-control study based on a cohort of 5443 Japanese-American men in Oahu, Hawaii, who had a physical examination and a phlebotomy during 1967 to 1970 [29].

References