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The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population.
Ohyauchi, M; Imatani, A; Yonechi, M; Asano, N; Miura, A; Iijima, K; Koike, T; Sekine, H; Ohara, S; Shimosegawa, T
[Miscellaneous Article] Gut. 54(3):330-335, March 2005.

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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-1[beta] or tumour necrosis factor [alpha].

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.