Association of interleukin 1 gene family polymorphisms with duodenal ulcer disease

Clin Exp Immunol. 2003 Dec;134(3):525-31. doi: 10.1111/j.1365-2249.2003.02325.x.


Cytokine genes taking part in the immunological response to Helicobacter pylori infection are good candidates to study for genetic predisposition to duodenal ulcer disease (DU). Among cytokines, interleukin (IL)-1beta and its natural specific inhibitor, the interleukin-1 receptor antagonist, are cytokines that play a key role in regulating gastric acid secretion and modulating the immune response in the gastrointestinal mucosa. We aimed to investigate whether polymorphisms in the IL-1B and IL-1RN genes are involved in the susceptibility to duodenal ulcer. DNA from 131 unrelated Spanish Caucasian patients with DU and 105 ethnically matched healthy controls was typed for the IL-1B-511, IL-1B-31, and IL-1B + 3954 gene polymorphisms, and the VNTR polymorphism in intron 2 of the IL-1RN gene by polymerase chain reaction (PCR)-based methods and TaqMan assays. H. pylori status and non-steroidal anti-inflammatory drugs (NSAIDs) use was determined in all patients and controls. Logistic regression analysis identified H. pylori infection (OR: 9.74; 95%CI = 3.53-26.89) and NSAIDs use (OR: 8.82; 95%CI = 3.51-22.17) as independent risk factors for DU. In addition, the simultaneous carriage of IL-1RN*2, IL-1B-511*C, IL-1B-31*T and IL-1B + 3954*C alleles was a genetic risk factor for DU in patients with H. pylori infection (OR: 3.22; 95%CI = 1.09-9.47). No significant differences in IL-1RN and IL-1B genotypes were found when patients were categorized according to gender, age of onset, smoking habit, NSAIDs use, type of complication and positive family history. Our results provide further evidence that host genetic factors play a key role in the pathogenesis of duodenal ulcer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Case-Control Studies
  • Chi-Square Distribution
  • Duodenal Ulcer / etiology
  • Duodenal Ulcer / genetics*
  • Duodenal Ulcer / immunology*
  • Female
  • Genetic Predisposition to Disease
  • Helicobacter Infections / complications
  • Helicobacter Infections / genetics
  • Helicobacter Infections / immunology
  • Helicobacter pylori
  • Humans
  • Interleukin-1 / genetics*
  • Linkage Disequilibrium
  • Logistic Models
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods
  • Polymorphism, Genetic*
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / genetics
  • Risk Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1
  • Receptors, Interleukin-1