IAI Accepts, published online ahead of print on 23 February 2009

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Infect. Immun. doi:10.1128/IAI.01284-08
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Differences in the genome content between H. pylori isolates from gastritis, duodenal ulcer or gastric cancer reveal novel disease associated genes

Carolina Romo-González, Nina R. Salama, Juan Burgeño-Ferreira, Veronica Ponce-Castañeda, Eduardo Lazcano-Ponce, Margarita Camorlinga-Ponce, and Javier Torres^*

Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, Centro Medico Nacional-Siglo XXI, Instituto Mexicano del Seguro Social, México, DF, México; Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Estadistica. Campus Montecillo. Colegio de Posgraduados, Montecillo, Estado de México, México; Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Publica. Cuernavaca, Morelos, México

^* To whom correspondence should be addressed. Email: jtorresl57{at}yahoo.com.mx.

H. 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 like 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 non-atrophic gastritis, 10 with Duodenal Ulcer, and 9 with Gastric Cancer were studied. Multiple isolates from the same patient were analysed by RAPD 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 in gastric cancer isolates. Thirty genes were significantly associated with non-atrophic gastritis, duodenal ulcer or gastric cancer of which 14 (46.6%) 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.