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Infection and Immunity, May 2009, p. 2201-2211, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01284-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Differences in Genome Content among Helicobacter pylori Isolates from Patients with Gastritis, Duodenal Ulcer, or Gastric Cancer Reveal Novel Disease-Associated Genes{triangledown} ,{dagger}

Carolina Romo-González,1,2 Nina R. Salama,3 Juan Burgeño-Ferreira,4 Veronica Ponce-Castañeda,1 Eduardo Lazcano-Ponce,5 Margarita Camorlinga-Ponce,1 and Javier Torres1*

Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, Centro Medico Nacional-Siglo XXI, Instituto Mexicano del Seguro Social, México DF, México,1 Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México,2 Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington,3 Estadistica, Campus Montecillo, Colegio de Posgraduados, Montecillo, Estado de México, México,4 Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Publica, Cuernavaca, Morelos, México5

Received 20 October 2008/ Returned for modification 21 November 2008/ Accepted 17 February 2009

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.

* Corresponding author. Mailing address: Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, Centro Medico Nacional-Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Av. Cuauhtemoc 330, México DF CP 06725, México. Phone: 555 627-6940. Fax: 555 627-6949. E-mail: jtorresl57{at}yahoo.com.mx

{triangledown} Published ahead of print on 23 February 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: B. A. McCormick

Infection and Immunity, May 2009, p. 2201-2211, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01284-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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