We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-γ Production and is Associated with Helicobacter pylori-induced Gastric Disease.
- Authors
Yang, Chin‐An; Scheibenbogen, Carmen; Bauer, Sandra; Kleinle, Christoph; Wex, Thomas; Bornschein, Jan; Malfertheiner, Peter; Hellmig, Stephan; Schumann, Ralf R.; Hamann, Lutz
- Abstract
Background Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 10-20% develop peptic ulcers and <3% progress to gastric cancer ( GC). Th1-predominant immune responses have been suggested to underlie H. pylori-induced gastric diseases. However, the reason for a strong inter-individual variation of susceptibility and course of the disease is currently far from being understood. It has been shown that H. pylori stimulates the host's Toll-like receptor ( TLR) 2/1 complex. Furthermore, the single nucleotide polymorphism ( SNP) I602S of TLR1 alters the inflammatory cytokine response of monocytes. Therefore, we hypothesized an association of this TLR1 SNP with H. pylori-mediated gastric pathologies. Materials and Methods Subjects with different TLR1 genotypes were analyzed for their IFN-γ response of NK- and T-cells. We further genotyped 548 patients with gastric diseases for this SNP and compared patients with gastritis with those having ulcer, and patients with high-risk gastritis versus patients with GC. Results Homozygous 602S allele carriers exhibited impaired in vitro IFN-γ responses to the TLR2/1 agonist Pam3 CSK4. The TLR1 I602S SNP is significantly associated with GC ( p = .002) and gastric ulcer ( p = .051). Odds ratios showed significantly reduced risk regarding GC and peptic ulcer for the homozygous mutated genotype. The odds ratios were 0.4 (95% CI, 0.22-0.72) and 0.588 (95% CI, 0.35-1.00), respectively. Conclusion In conclusion, our results suggest that the nonfunctional TLR1 602S/S genotype is associated with a reduced risk of H. pylori-induced gastric diseases, probably via diminished Th1 responses.
- Subjects
GASTRIC mucosa; GENETICS of disease susceptibility; GENETIC polymorphisms; IMMUNE response; TOLL-like receptors; HELICOBACTER pylori; PEPTIC ulcer; CANCER
- Publication
Helicobacter, 2013, Vol 18, Issue 1, p13
- ISSN
1083-4389
- Publication type
Article
- DOI
10.1111/hel.12001