Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1β production in Helicobacter pylori infection

Il Ran Hwang, Tadashi Kodama, Shogo Kikuchi, Kyoko Sakai, Leif E. Peterson, David Y. Graham, Yoshio Yamaoka

Research output: Contribution to journalArticle

322 Scopus citations

Abstract

Background & Aims: Although epidemiological studies suggest that interleukin (IL)-1 genetic polymorphisms are involved in Helicobacter pylori-related gastric carcinogenesis, the data are conflicting regarding the effects of these polymorphisms on IL-1β production. Methods: IL-1B-511 polymorphism was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and IL-1RN variable number of tandem repeats was determined by PCR. Mucosal IL-1β levels were measured by enzyme-linked immunosorbent assay. To determine which factors influence mucosal IL-1β levels, gastric inflammation, and atrophy, multiple regression analyses were performed. Results: We studied 117 H. pylori-infected Japanese patients. Carriers of the IL-1B-511T/T genotype or IL-1RN*2 allele had higher mucosal IL-1β levels than noncarriers (partial regression coefficient [PRC] ± SE), TT versus CC: 37.6 ± 6 [antrum] and 32.1 ± 6 [corpus] pg/mg protein (P < 0.001 for each), *1/*2 versus *1/*1: 24 ± 8 [antrum] (P <0.01) and 36.5 ± 7 [corpus] (P <0.001). Simultaneous carriers of IL-1B-511T/T genotype and IL-1RN*2 allele had the highest IL-1β levels (82.9 ± 12 [antrum] and 87.2 ± 11 [corpus]) and showed a synergistic effect between 2 loci. The ±1/±2 carriers were closely related to atrophy (PRC ± SE; 0.87 ± 0.4 [antrum] and 0.93 ± 0.4 [corpus], P < 0.05), whereas being a carrier of the -511T/T genotype was related to severe gastric inflammation. Conclusions: IL-1 genetic polymorphisms influenced H. pylori-related gastric mucosal IL-1β levels and were related to gastric inflammation and atrophy, factors thought to be important in gastric carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1793-1803
Number of pages11
JournalGastroenterology
Volume123
Issue number6
DOIs
StatePublished - Dec 1 2002

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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