BACKGROUND AND AIMS: Chronic H. pylori infection is the main cause of ulcer disease which depicts a major burden of our healthy care systems. The individual host immune response plays a pivotal role in the outcome of the infection but genetic susceptibility to develop gastric ulcer is unknown. IL-1beta and its natural receptor antagonist IL-1ra are involved in the inflammatory response to H. pylori infection. Thus, we investigated the influence of functional genetic variants in the IL-1 gene cluster on the development of gastric ulcer disease. PATIENTS AND METHODS: 390 H. pylori infected patients were genotyped for IL-1B -31 and +3954 by TaqMan technology. Alleles of IL-1RN 86VNTR were determined by gel electrophoresis after amplification. Three hundred and sixty healthy blood donors were included as healthy controls. RESULTS: Carriage of the IL-1B -31 C allele conferred a increased but not significant risk for H. pylori infection (OR: 1.3, Wald 95% CI: 0.8<OR<2.1). Patients carrying short allele 2 of IL-1RN had a 1.6-fold significantly increased risk for the development of gastric ulcer (Pearson's=4.0, p=0.044, OR: 1.6, Wald 95% CI: 1.0<OR<2.4). CONCLUSION: Our results underline the crucial role of the host immune response to H. pylori infection and confirm the importance of polymorphisms in the IL-1 cluster as a factor to give rise to different clinical outcomes. Further studies are needed to fully understand the pathophysiological effect of polymorphisms in the IL-1 cluster in H. pylori associated ulcer disease and susceptibility to infection itself.
BACKGROUND AND AIMS: Chronic H. pylori infection is the main cause of ulcer disease which depicts a major burden of our healthy care systems. The individual host immune response plays a pivotal role in the outcome of the infection but genetic susceptibility to develop gastric ulcer is unknown. IL-1beta and its natural receptor antagonist IL-1ra are involved in the inflammatory response to H. pylori infection. Thus, we investigated the influence of functional genetic variants in the IL-1 gene cluster on the development of gastric ulcer disease. PATIENTS AND METHODS: 390 H. pyloriinfectedpatients were genotyped for IL-1B -31 and +3954 by TaqMan technology. Alleles of IL-1RN 86VNTR were determined by gel electrophoresis after amplification. Three hundred and sixty healthy blood donors were included as healthy controls. RESULTS: Carriage of the IL-1B -31 C allele conferred a increased but not significant risk for H. pylori infection (OR: 1.3, Wald 95% CI: 0.8<OR<2.1). Patients carrying short allele 2 of IL-1RN had a 1.6-fold significantly increased risk for the development of gastric ulcer (Pearson's=4.0, p=0.044, OR: 1.6, Wald 95% CI: 1.0<OR<2.4). CONCLUSION: Our results underline the crucial role of the host immune response to H. pylori infection and confirm the importance of polymorphisms in the IL-1 cluster as a factor to give rise to different clinical outcomes. Further studies are needed to fully understand the pathophysiological effect of polymorphisms in the IL-1 cluster in H. pylori associated ulcer disease and susceptibility to infection itself.
Authors: Samuel B Ferreira; Ana Paula F Trombone; Carlos E Repeke; Cristina R Cardoso; Walter Martins; Carlos F Santos; Paula Cristina Trevilatto; Mario J Avila-Campos; Ana Paula Campanelli; João S Silva; Gustavo P Garlet Journal: Infect Immun Date: 2008-06-09 Impact factor: 3.441