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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
Author(s) -
Yang ChinAn,
Scheibenbogen Carmen,
Bauer Sandra,
Kleinle Christoph,
Wex Thomas,
Bornschein Jan,
Malfertheiner Peter,
Hellmig Stephan,
Schumann Ralf R.,
Hamann Lutz
Publication year - 2013
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1111/hel.12001
Subject(s) - single nucleotide polymorphism , helicobacter pylori , snp , odds ratio , genotype , gastritis , immunology , allele , medicine , immune system , gastroenterology , disease , biology , gene , genetics
Background H elicobacter 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 TLR 1 alters the inflammatory cytokine response of monocytes. Therefore, we hypothesized an association of this TLR 1 SNP with H . pylori ‐mediated gastric pathologies. Materials and Methods Subjects with different TLR 1 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 TLR 2/1 agonist Pam 3 CSK 4 . The TLR 1 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 TLR 1 602S/S genotype is associated with a reduced risk of H . pylori ‐induced gastric diseases, probably via diminished Th1 responses.