A Frequent Toll-Like Receptor 1 Gene Polymorphism Affects NK- and T-cell IFN-gamma Production and is Associated with Helicobacter pylori-induced Gastric Disease

作者：Yang Chin An; Scheibenbogen Carmen; Bauer Sandra; Kleinle Christoph; Wex Thomas; Bornschein Jan; Malfertheiner Peter; Hellmig Stephan; Schumann Ralf R; Hamann Lutz^*

来源：Helicobacter, 2013, 18(1): 13-21.

DOI：10.1111/hel.12001

• Gastric cancer
• genetic susceptibility
• immune response
• peptic ulcer

Background Helicobacter pylori infects approximately 50% of the world population. Among the infected individuals, only 1020% develop peptic ulcers and <3% progress to gastric cancer (GC). Th1-predominant immune responses have been suggested to underlie H.similar to 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.similar to 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.similar to pylori-mediated gastric pathologies. Materials and Methods Subjects with different TLR1 genotypes were analyzed for their IFN-? 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-? responses to the TLR2/1 agonist Pam3CSK4. The TLR1 I602S SNP is significantly associated with GC (p similar to=similar to.002) and gastric ulcer (p similar to=similar to.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, 0.220.72) and 0.588 (95% CI, 0.351.00), respectively. Conclusion In conclusion, our results suggest that the nonfunctional TLR1 602S/S genotype is associated with a reduced risk of H.similar to pylori-induced gastric diseases, probably via diminished Th1 responses.

• 出版日期2013-2
• 单位河北医科大学