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Differences in genome content among Helicobacter pylori isolates from patients with gastritis, duodenal ulcer, or gastric cancer reveal novel disease-associated genes.

ABSTRACT: Helicobacter pylori establishes a chronic infection in the human stomach, causing gastritis, peptic ulcer, or gastric cancer, and more severe diseases are associated with virulence genes such as the cag pathogenicity island (PAI). The aim of this work was to study gene content differences among H. pylori strains isolated from patients with different gastroduodenal diseases in a Mexican-Mestizo patient population. H. pylori isolates from 10 patients with nonatrophic gastritis, 10 patients with duodenal ulcer, and 9 patients with gastric cancer were studied. Multiple isolates from the same patient were analyzed by randomly amplified polymorphic DNA analysis, and strains with unique patterns were tested using whole-genome microarray-based comparative genomic hybridization (aCGH). We studied 42 isolates and found 1,319 genes present in all isolates, while 341 (20.5%) were variable genes. Among the variable genes, 127 (37%) were distributed within plasticity zones (PZs). The overall number of variable genes present in a given isolate was significantly lower for gastric cancer isolates. Thirty genes were significantly associated with nonatrophic gastritis, duodenal ulcer, or gastric cancer, 14 (46.6%) of which were within PZs and the cag PAI. Two genes (HP0674 and JHP0940) were absent in all gastric cancer isolates. Many of the disease-associated genes outside the PZs formed clusters, and some of these genes are regulated in response to acid or other environmental conditions. Validation of candidate genes identified by aCGH in a second patient cohort allowed the identification of novel H. pylori genes associated with gastric cancer or duodenal ulcer. These disease-associated genes may serve as biomarkers of the risk for severe gastroduodenal diseases.

SUBMITTER: Romo-Gonzalez C

PROVIDER: S-EPMC2681767 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Differences in genome content among Helicobacter pylori isolates from patients with gastritis, duodenal ulcer, or gastric cancer reveal novel disease-associated genes.

Romo-González Carolina C Salama Nina R NR Burgeño-Ferreira Juan J Ponce-Castañeda Veronica V Lazcano-Ponce Eduardo E Camorlinga-Ponce Margarita M Torres Javier J

Infection and immunity 20090223 5

Helicobacter pylori establishes a chronic infection in the human stomach, causing gastritis, peptic ulcer, or gastric cancer, and more severe diseases are associated with virulence genes such as the cag pathogenicity island (PAI). The aim of this work was to study gene content differences among H. pylori strains isolated from patients with different gastroduodenal diseases in a Mexican-Mestizo patient population. H. pylori isolates from 10 patients with nonatrophic gastritis, 10 patients with du ...[more]

PMID: 19237517

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Project description:BACKGROUND:Helicobacter pylori (H. pylori) represents a key factor in the etiology of autoimmune atrophic gastritis (AAG), duodenal ulcer (DU) and gastric cancer (GC). The aim of this study was to characterize the differential protein expression of H. pylori isolated from gastric biopsies of patients affected by either AAG, DU or GC. METHODS:The H. pylori strains were isolated from endoscopic biopsies from the stomach of patients with gastric disease. Protein profiles of H. pylori were compared by two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) for the identification of significantly different spots (Student t-test, p?<?0.05). RESULTS:A total of 47 differentially expressed spots were found between H. pylori isolated from patients with either DU or AAG diseases and those isolated from patients with GC (Anova?<?0.05, log fold change >1.5). These spots corresponded to 35 unique proteins. The identity of 7 protein spots was validated after one-dimensional electrophoresis and MS/MS analyses of excised gel portions. In H. pylori isolated from DU-patients a significant increase in proteins with antioxidant activity emerged (AroQ, AspA, FldA, Icd, OorA and ScoB), together with a higher content of proteins counteracting the high acid environment (KatA and NapA). In H. pylori isolated from AAG-patients proteins neutralizing hydrogen concentrations through organic substance metabolic processes decreased (GroL, TrxB and Tuf). In addition, a reduction of bacterial motility (FlhA) was found to be associated with AAG-H. pylori isolates. In GC-H. pylori strains it was found an increase in nucleic acid-binding proteins (e.g. DnaG, Tuf, RpoA, RplU) which may be involved in a higher demand of DNA- and protein-related processes. CONCLUSION:Our data suggest the presence of specific protein signatures discriminating among H. pylori isolated from either AAG, DU or GC. Changes in protein expression profiles evaluated by DIGE succeeded in deciphering part of the molecular scenarios associated with the different H. pylori-related gastric diseases.

Project description:BACKGROUND: The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to Helicobacter pylori varies by population and geographic area.Our objective was to determine if the IL-1B -511 T>C and -31 C>T polymorphisms and H. pylori vacA genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population. METHODS: We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. H. pylori infection and vacA genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-H. pylori serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the IL-1B -511 T>C polymorphism was genotyped by PCR-RFLPs and the IL-1B -31 C>T polymorphism was genotyped by pyrosequencing. RESULTS: Sixty-two point seven (62.7%) of the 102 control subjects were H. pylori-seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were H. pylori-positive. The predominant H. pylori genotype was vacA s1m1 (58.4%) and the most frequent subtype was vacA s1. The -511 TC, (rs16944 -511 T>C) genotype and the -511C allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -31T (rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The IL-1B -511C/-31T haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer. CONCLUSIONS: The H. pylori vacA genotypes identified herein were similar to those reported for other regions of Mexico. The vacA s1m1 genotype was not associated with gastric ulcer. In the southern Mexican population, the IL-1B -511C and -31T alleles and the -511C/-31T and -511T/-31T haplotypes are associated with increased risk of chronic gastritis and gastric ulcer.

Project description:Background and Objective: Helicobacter pylori is a human-stomach-dwelling organism that causes many gastric illnesses, including gastritis, ulcer, and gastric cancer. The purpose of the study was to perform differential proteomic analysis on H. pylori isolates from gastritis, ulcer, and gastric cancer patients. Materials and Methods: H. pylori was isolated from antrum and fundus biopsies obtained from patients who visited the Department of Gastroenterology. Using nano-LC-QTOF MS/MS analysis, differentially regulated proteins were identified through proteome profiling of pooled samples of H. pylori isolated from gastritis, ulcer, and gastric cancer patients. Antigenic scores and cellular localization of proteins were determined using additional prediction tools. Results: A total of 14 significantly regulated proteins were identified in H. pylori isolated from patients with either gastritis, ulcer, or gastric cancer. Comparative analysis of groups revealed that in the case of cancer vs. gastritis, six proteins were overexpressed, out of which two proteins, including hydrogenase maturation factor (hypA) and nucleoside diphosphate kinase (ndk) involved in bacterial colonization, were only upregulated in isolates from cancer patients. Similarly, in cancer vs. ulcer, a total of nine proteins were expressed. Sec-independent protein translocase protein (tatB), involved in protein translocation, and pseudaminic acid synthase I (pseI), involved in the synthesis of functional flagella, were upregulated in cancer, while hypA and ndk were downregulated. In ulcer vs. gastritis, eight proteins were expressed. In this group, tatB was overexpressed. A reduction in thioredoxin peroxidase (bacterioferritin co-migratory protein (bcp)) was observed in ulcer vs. gastritis and cancer vs. ulcer. Conclusion: Our study suggested three discrete protein signatures, hypA, tatB, and bcp, with differential expression in gastritis, ulcer, and cancer. Protein expression profiles of H. pylori isolated from patients with these gastric diseases will help to understand the virulence and pathogenesis of H. pylori.

Dataset Information

Differences in genome content among Helicobacter pylori isolates from patients with gastritis, duodenal ulcer, or gastric cancer reveal novel disease-associated genes.

Publications

Differences in genome content among Helicobacter pylori isolates from patients with gastritis, duodenal ulcer, or gastric cancer reveal novel disease-associated genes.

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