Interleukin 1beta polymorphisms increase risk of hypochlorhydria and atrophic gastritis and reduce risk of duodenal ulcer recurrence in Japan.
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.
Furuta
Takahisa
T
First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. furutat@mail.nih.gov
El-Omar
Emad M
EM
Xiao
Fang
F
Shirai
Naohito
N
Takashima
Misako
M
Sugimura
Haruhiko
H
Sugimurra
Haruhiko
H
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
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D020115:Pepsinogen C; D020116:Pepsinogen A