title: Synergistic effect of IL-1β and TNF-α polymorphisms on the H. pylori-related gastric pre-malignant condition.
abstract: OBJECTIVE
  We investigated the effect of IL-1β and TNF-α polymorphisms, and its synergistic effect with age, gender and H. pylori status on the gastric pre-malignant condition.
  
  
  METHODS
  IL-1β-31(T>C) and -511(C>T) and TNF-α-857 (C>T) polymorphisms were genotyped in 123 cancer free subjects. Degree of histological gastritis in both antrum and corpus, and extension of endoscopic gastric atrophy were also evaluated.
  
  
  RESULTS
  Significant associations were found between degrees of mononuclear cell infiltration (p=0.007) and atrophy (p=0.01) in the antrum with IL-1β-31(T>C) polymorphism, and degree of endoscopic gastric atrophy with both IL-1β-31(T>C), -511(C>T) polymorphisms (p=0.03, 0.04, respectively). When subjects were divided into the 3 groups according to the histological severity of gastric mucosal atrophy: the non-atrophic gastritis (NA) group (atrophy score=0 and metaplasia score=0), the severe atrophic gastritis (SA) group (atrophy score>=2 or metaplasia score>=2), and the mild atrophic gastritis (MA) group (all others), synergistic effect was found between numbers of IL-1β-31C, IL-1β-511T variant alleles with co-factors on the development of gastric atrophy in the antrum (gender + H. pylori + number of IL-1β-31C allele: p=0.001, age + gender + H. pylori + number of IL-1β-31C allele: p=0.0008, gender + H. pylori + number of IL-1β-511T allele: p=0.016, age + gender + H. pylori + number of IL-1β-511T allele: p=0.013), while such association was found for TNF-α-857 T allele in the antrum and all genotypes in the corpus.
  
  
  CONCLUSIONS
  IL-1β-31C, IL-1β-511T variant alleles may accelerate gastric mucosal inflammation and atrophy, not only by themselves, but also through the interaction with co-factors.
authors.affiliation: Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Japan. tomomiccyu@yahoo.co.jp
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yamashita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Okubo
authors.forename: Joh
authors.initials: J
authors.lastname: Yonemura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Masami
authors.initials: M
authors.lastname: Iwata
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001284:Atrophy; D001706:Biopsy; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005773:Gastroscopy; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000302:isolation & purification*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011706:Pyloric Antrum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D013274:Stomach Neoplasms / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha