title: The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population.
abstract: BACKGROUND
  Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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-1beta 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.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan. moyauchi@int3.med.tohoku.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Ohyauchi
authors.forename: A
authors.initials: A
authors.lastname: Imatani
authors.forename: M
authors.initials: M
authors.lastname: Yonechi
authors.forename: N
authors.initials: N
authors.lastname: Asano
authors.forename: A
authors.initials: A
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Iijima
authors.forename: T
authors.initials: T
authors.lastname: Koike
authors.forename: H
authors.initials: H
authors.lastname: Sekine
authors.forename: S
authors.initials: S
authors.lastname: Ohara
authors.forename: T
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D004381:Duodenal Ulcer / Q000382:microbiology; D005260:Female; D005756:Gastritis / Q000382:microbiology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013272:Stomach Diseases / Q000382:microbiology*; D013274:Stomach Neoplasms / Q000382:microbiology; D013276:Stomach Ulcer / Q000382:microbiology
chemical_list: D016209:Interleukin-8