Genetic polymorphisms of NOD1 and IL-8, but not polymorphisms of TLR4 genes, are associated with Helicobacter pylori-induced duodenal ulcer and gastritis

Helicobacter. 2007 Apr;12(2):124-31. doi: 10.1111/j.1523-5378.2007.00481.x.

Abstract

Background: Intracellular pathogen receptor NOD1 is involved in the epithelial cell sensing Helicobacter pylori, which results in a considerable interleukin (IL)-8 production. The aim of this study was to evaluate the relationship between NOD1 and IL-8 genetic polymorphisms and the development of H. pylori-induced gastritis and duodenal ulcer (DU), as compared with TLR4 polymorphisms.

Materials and methods: Eighty-five patients with DU and 135 patients with gastritis were enrolled in the study. Seventy-five serologically H. pylori-positive subjects without gastric or duodenal symptoms served as controls. The G796A (E266K) NOD1 polymorphism was determined by restriction fragment length polymorphism, and the -251 IL-8 polymorphism by amplification refractory mutation system method. The TLR4 (ASP/299/Gly and Thr/399/Ile) gene polymorphisms were examined by melting point analysis.

Results: AA homozygote mutant variants of NOD1 were detected in 20% of the H. pylori-positive patients with DU versus 7% of H. pylori-positive patients with gastritis and versus 6% of the H. pylori-positive healthy controls. The IL-8 heterozygote mutant variant was detected with a significantly higher frequency among the DU patients and those with gastritis than among the H. pylori-positive controls. However, no significant correlation concerning the frequency of the TLR4 gene polymorphism could be revealed between any group of patients and the controls.

Conclusion: E266K CARD4/NOD1, but not the TLR4 gene polymorphism increases the risk of peptic ulceration in H. pylori-positive patients. The -251 IL-8 polymorphism was significantly associated with either gastritis or DU in H. pylori-infected subjects. Host factors including intracellular pathogen receptors and IL-8 production play an important role in H. pylori-induced gastric mucosal damage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Duodenal Ulcer / genetics*
  • Duodenal Ulcer / microbiology
  • Gastritis / genetics*
  • Gastritis / microbiology
  • Genetic Predisposition to Disease
  • Helicobacter Infections / genetics*
  • Helicobacter pylori / pathogenicity
  • Humans
  • Interleukin-8 / genetics*
  • Nod1 Signaling Adaptor Protein / genetics*
  • Polymorphism, Genetic
  • Toll-Like Receptor 4 / genetics*

Substances

  • Interleukin-8
  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • TLR4 protein, human
  • Toll-Like Receptor 4