title: The Helicobacter pylori plasticity region locus jhp0947-jhp0949 is associated with duodenal ulcer disease and interleukin-12 production in monocyte cells.
abstract: Colonization with Helicobacter pylori always results in chronic gastritis, which is controlled by infiltration of mononuclear cells and the subsequent release of cytokines like interleukin (IL)-12. To identify H. pylori factors involved in inducing cytokine production in mononuclear cells, a random H. pylori mutant library was screened for the inability to induce IL-12 production in monocyte THP-1 cells. Of the 231 random mutants screened, one mutant (M1) showed a consistent twofold decrease in the amount of IL-12 induction compared to the parental strain 1061 (P <0.01). Further characterization of mutant M1 revealed that the kanamycin resistance cassette had integrated in the jhp0945 gene, which is situated in an H. pylori strain-specific plasticity region. Three reference strains possessing this plasticity region induced significantly higher amounts of IL-12 when compared to the H. pylori 26695 reference strain, which does not possess this plasticity region. The role in disease outcome of jhp0945 as well as the neighbouring plasticity region genes jhp0947 and jhp049 was assessed in a Dutch population cohort. Firstly, the presence of jhp0947 was completely linked with that of jhp0949 and was roughly associated with jhp0945 (P=0.072), but not with the cag pathogenicity island (PAI) (P=0.464). The presence of the jhp0947 and jhp0949 genes, but not of jhp0945, was significantly associated with duodenal ulcer disease when compared to gastritis (P=0.027). Therefore, the jhp0947-jhp0949 locus may be a novel putative H. pylori marker for disease outcome independent of the cag PAI.
authors.affiliation: Department of Gastroenterology and Hepatology, Room L-459, Erasmus MC-University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
authors.forename: Ramon
authors.initials: R
authors.lastname: de Jonge
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Sabine C L
authors.initials: SC
authors.lastname: Langeveld
authors.forename: Ruud J L F
authors.initials: RJ
authors.lastname: Loffeld
authors.forename: Jeroen
authors.initials: J
authors.lastname: Stoof
authors.forename: Arnoud H M
authors.initials: AH
authors.lastname: van Vliet
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Kusters
mesh_terms: D002478:Cells, Cultured; D015331:Cohort Studies; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004381:Duodenal Ulcer / Q000276:immunology / Q000382:microbiology*; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D016480:Helicobacter pylori / Q000235:genetics* / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D007613:Kanamycin Resistance / Q000235:genetics; D016015:Logistic Models; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016254:Mutagenesis, Insertional; D009426:Netherlands; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial; D018664:Interleukin-12