Influence of IL-1 gene cluster polymorphisms on the development of H. pylori associated gastric ulcer

Abstract

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-1β 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.