title: Synergistic effect of Helicobacter pylori virulence factors and interleukin-1 polymorphisms for the development of severe histological changes in the gastric mucosa.
abstract: Polymorphisms of the IL-1B and IL-1RN genes (which encode interleukin [IL]-1beta and IL-1 receptor antagonist, respectively) have been associated with hypochlorhydria and gastric cancer. We investigated the influence of bacterial virulence factors and host IL-1 polymorphisms on the development of histologic abnormalities in 210 Helicobacter pylori-infected patients with chronic gastritis. cagA(+)/vacAs1(+) H. pylori strains were associated with intestinal metaplasia (IM), atrophic gastritis (AG), and severe inflammation. Carriers of the proinflammatory IL-1B -511T/-31C and IL-1RN*2 alleles had an increased risk for the development of AG, IM, and severe inflammation, with odds ratios (ORs) of 1.7 (95% confidence interval [CI], 0.8-3.4) to 4.4 (95% CI, 1.5-12.9). The highest prevalence of severe gastric abnormalities was found in patients with both host and bacterial high-risk genotypes (cagA(+)/vacAs1(+)/IL-1B -511T/IL-1RN*2), with ORs of 24.8 (95% CI, 5.2-117.3) for severe lymphocytic infiltration, 9.5 (95% CI, 2.8-32.1) for severe granulocytic infiltration, 6.0 (95% CI, 2.4-15.5) for IM, and 2.4 (95% CI, 0.93-6.2) for AG. Combined bacterial/host genotyping thus may provide a clinical tool to identify patients at high risk of developing cancer.
authors.affiliation: Department of Internal Medicine II and Gastroenterology, Bogenhausen Academic Teaching Hospital, Technical University of Munich, Ismaningerstrasse 22, 81675 Munich, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.forename: Christian
authors.initials: C
authors.lastname: Prinz
authors.forename: Bruno
authors.initials: B
authors.lastname: Neu
authors.forename: Mathilde
authors.initials: M
authors.lastname: Neuhofer
authors.forename: Marco
authors.initials: M
authors.lastname: Zeitner
authors.forename: Petra
authors.initials: P
authors.lastname: Voland
authors.forename: Ingrid
authors.initials: I
authors.lastname: Becker
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schepp
authors.forename: Markus
authors.initials: M
authors.lastname: Gerhard
mesh_terms: D000328:Adult; D000483:Alleles; D005753:Gastric Mucosa / Q000382:microbiology* / Q000473:pathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D016481:Helicobacter Infections / Q000235:genetics* / Q000473:pathology*; D016480:Helicobacter pylori / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D013270:Stomach / Q000382:microbiology; D013272:Stomach Diseases / Q000235:genetics / Q000382:microbiology; D014774:Virulence
chemical_list: D007375:Interleukin-1