title: Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan.
abstract: OBJECTIVE
  Interleukin-1 beta (IL-1beta) polymorphisms are associated with increased risk of gastric cancer in whites. This study aimed to examine effects of these polymorphisms on gastric acid secretion, atrophic gastritis, and risk of peptic ulcer in Japan.
  
  
  METHODS
  We determined IL-1B-511/-31 and IL-1RN genotypes and measured gastric juice pH, serum pepsinogen (PG) I and II levels, and gastritis and atrophy scores in Helicobacter pylori-positive patients with gastritis only, gastric ulcers, or duodenal ulcers (DUs), and H. pylori-negative controls.
  
  
  RESULTS
  In the H. pylori-positive group, subjects with the proinflammatory IL-1B-511 T/T genotype had the highest atrophy and gastritis scores, the highest median gastric juice pH, and the lowest median serum PG I/PG II ratios. Although gastric juice pH significantly increased and serum PG I and PG I/PG II ratios significantly decreased in the IL-1B-511 T/T genotype group with age, no such age-dependent changes were observed in the C/C genotype group. Changes in the C/T genotype group were intermediate. In the H. pylori-negative group, the IL-1 loci had no effect on any of the physiologic or morphologic parameters. Carriage of IL-1RN allele 2 significantly protected against DU disease while the IL-1B-511 T/T genotype significantly protected against DU recurrence in patients older than 60 years.
  
  
  CONCLUSIONS
  Proinflammatory IL-1beta polymorphisms are associated with hypochlorhydria and atrophic gastritis in Japan. The effects are dependent on H. pylori infection and become more significant with advancing age. This may explain the high incidence of gastric cancer in Japan and also the age-dependent decrease in DU recurrence in infected subjects.
authors.affiliation: First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. furutat@mail.nih.gov
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furuta
authors.forename: Emad M
authors.initials: EM
authors.lastname: El-Omar
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.forename: Naohito
authors.initials: N
authors.lastname: Shirai
authors.forename: Misako
authors.initials: M
authors.lastname: Takashima
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimurra
mesh_terms: D000126:Achlorhydria / Q000235:genetics*; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D004381:Duodenal Ulcer / Q000235:genetics*; D005260:Female; D005750:Gastric Juice / Q000737:chemistry; D005757:Gastritis, Atrophic / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D020115:Pepsinogen C / Q000097:blood; D010437:Peptic Ulcer / Q000235:genetics; D011110:Polymorphism, Genetic; D012008:Recurrence; D012795:Sialoglycoproteins / Q000235:genetics
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D020115:Pepsinogen C; D020116:Pepsinogen A