The polymorphism interleukin 8 - 251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population

M. Ohyauchi, A. Imatani, M. Yonechi, N. Asano, A. Miura, K. Iijima, T. Koike, H. Sekine, S. Ohara, T. Shimosegawa

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191 Citations (Scopus)

Abstract

Background: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. Aims: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. Subjects: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. Methods: We identified the IL-8 - 251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. Results: IL-8 - 251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 - 251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in -251A carriers than in T/T carriers. In the in vitro assay, IL-8 - 251A showed enhanced promoter activity in response to IL-1β or tumour necrosis factor α. Conclusions: The IL-8 - 251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.

Original languageEnglish
Pages (from-to)330-335
Number of pages6
JournalGut
Volume54
Issue number3
DOIs
Publication statusPublished - 2005 Mar

ASJC Scopus subject areas

  • Gastroenterology

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