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 Printable version |
Genetic polymorphism of interleukin-8 (IL-8) is associated with Helicobacter pylori-induced duodenal ulcer |
European Cytokine Network. Volume 15, Number 4, 353-8, December 2004, Research papers
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 Free Article
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Author(s) : Zsofia Gyulai, Gergely Klausz, Andrea Tiszai, Zsuzsanna Lénárt, Izabella Tóth Kása, János Lonovics, Yvette Mándi |
Summary : Background and aims. Helicobacter pylori infection almost invariably causes chronic gastritis, but only a proportion of the infected subjects develop peptic ulcers. The local inflammation associated with H. pylori infection is characterized by an increased production of the proinflammatory cytokines IL-1–B, IL-6, IL-8 and TNF-α. Since such cytokine production is often determined by the genetic polymorphism of regions regulating cytokine gene expression, we investigated the relationship between TNF-α and IL-8 polymorphisms and the development of duodenal ulcer disease. We also sought a correlation between the promoter polymorphism of the lipopolysaccharide (LPS) receptor CD14 and the formation of peptic ulcer, because CD14 plays a crucial role in the initiation of the cytokine cascade. Methods. Genomic DNA extracted from the peripheral blood of 69 patients with H. pylori-positive duodenal ulcer disease and 47 H. pylori-positive healthy controls was analyzed for TNF-α -308 promoter polymorphism by RFLP, and for IL-8 -251 polymorphism by ARMS. Genetic polymorphism within the promoter of the CD14 gene was identified using the LightCycler instrument via melting point analysis. Results: No significant correlation could be revealed between the TNF-α and CD14 promoter polymorphisms and the clinical outcome of H. pylori infection. The IL-8 A/T heterozygote mutant variant was detected with a significantly higher frequency (65.22%) among the ulcer patients than among the healthy, H. pylori-positive blood donors (36.17%), while the frequency of the normal allelic genotype (TT) was significantly higher in the control group (44.6% vs 15.9%). Conclusion. Analysis of the genetic predisposition to enhanced cytokine production revealed a significant association only for the IL-8 polymorphism. This observation draws attention to the possible importance of IL-8 polymorphism as a genetic predisposing factor in the pathomechanism of H. pylori-induced duodenal ulcer disease, and to the relative protection from duodenal ulcer disease that is associated with the TT genotype. |
Keywords : Helicobacter pylori, duodenal ulcer, genetic polymorphism, IL-8, TNF-α, CD-14 |
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