Analysis of the 3' Variable Region of Cytotoxin-Associated Gene A (<i>cagA</i>) in <i>Helicobacter pylori</i> Isolates in China

Abstract

Infection by the bacterium Helicobacter pylori is a putative cause of various gastric disorders, including gastric adenocarcinoma. Incident rates are associated with variants of the H. pylori virulence factor cytotoxin-associated gene A protein (CagA), encoded by the gene cagA. However, these variants have not been characterized in China, where gastric cancer is common. We investigated the diversity of CagA variants in H. pylori strains isolated from a Chinese population. The 3' variable region of cagA genes from 66 clinical isolates in China were amplified by polymerase chain reaction, sequenced, aligned, and analyzed. All 66 H. pylori strains were CagA-positive, of which 93.9% were East Asian type and the tyrosine phosphorylation motifs (TPMs) were EPIYA-ABD. The remainder was Western type, in which TPMs were EPIYA-ABC. Interestingly, two of sixty-two strains (3.2%) of the East Asian type were mutated into ESIYA-B, whereas all four Western type (100%) strains were mutated into EPIYT-B. Both of the two strains with Western-type CagA obtained from gastric cancer patients contained a distinguished mutation on the first residue following the EPIYA site in the EPIYA-A motif. The predominant CagA type in these H. pylori strains isolated from Chinese patients in China was East Asian, with TPMs EPIYA-ABD, and there existed mutations in both the East Asian and Western type CagA.

Expressions of the CagA protein and CagA-signaling molecules predict Helicobacter pylori dependence of early-stage gastric DLBCL

“…Our results also disclosed that the cagA gene can be detected in all gastric tumor biopsies obtained from 7 selective cases of HP-dependent gastric DLBCL whose tumor were expressing CagA (supplemental Methods; supplemental Figure 3). 73 In addition, among these HP-dependent gastric DLBCL tumors, downregulated expression of CagA and CagA-signaling molecules (p-SHP-2 and p-ERK) were found in post-HPE gastric biopsy samples. These findings suggest that CagA-regulated signaling might be involved in HP-dependent lymphomagenesis of gastric DLBCL.…”

Recent Updates of Helicobacter pylori Infection: from Epidemiology Study to Guideline Issues

“…From the prespective of the bacteria, virulence factors of CagA with East Asian type (EPIYA-D) present in Recent Updates of Helicobacter pylori Infection: from Epidemiology Study to Guideline Issues Chinese population, while Western type (EPIYA-C) predominantly occur in Indian population. 25,26 H. pylori also interacts with hosts who are susceptible to have chronic inflammation, atrophy of gastric mucosa, and development of cancer. Finally, many factors interact in the event of gastric cancer.…”

“…The diagnostic test of H. pylori can only be performed if there is a plan to offer a treatment for positive results. 26 Indications for treating H. pylori infection are also the same in these three guidelines; peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma (MALToma), atrophic gastritis, history of gastric cancer resection, history of gastric cancer in the family, patient's wishes, non-ulcer dyspepsia, before starting long-term aspirin therapy for high risk for ulcer patients, gastroesophageal reflux disease (GERD) requiring long-term proton pump inhibitor, and community prevention for gastric cancer in the region with high incidence of gastric cancer. 5 In ACG guideline, there is a separation of established and controversial indication for diagnostic and treatment of H. pylori infection, with the controversial indications are persons using non-steroidal anti-inflammatory drugs (NSAIDs), unexplained iron deficiency anemia, GERD, and non-ulcer dyspepsia.…”

“…[31][32][33] In these three guidelines, only Maasctrich consensus stated about the use of probiotics with the recommendation D (expert opinion without explicit critical appraisal or based on physiology, bench research or 'first principles'), while ACG and Asia Pacific guideline did not mention about probiotics at all. 26 The consensus stated thatcertain probiotics and prebiotics show promising results as an adjuvant treatment in reducing side effects.…”