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. Issue 1 (28th August 2012)

• Record Type: Journal Article
• Authors: Yang, Chin‐An; Scheibenbogen, Carmen; Bauer, Sandra; Kleinle, Christoph; Wex, Thomas; Bornschein, Jan; Malfertheiner, Peter; Hellmig, Stephan; Schumann, Ralf R.; Hamann, Lutz
• Is Part Of: Helicobacter. Volume 18:Issue 1(2013:Feb.)
• Page Start: 13
• Page End: 21
• Publication Date: 2012-08-28
• Subjects: Helicobacter -- Periodicals; Helicobacter infections -- Periodicals; Stomach -- Diseases -- Periodicals; 616.3301405
• DOI: 10.1111/hel.12001
• Languages: English
• ISSNs: 1083-4389

Abstract

<abstract abstract-type="main" id="hel12001-abs-0001"> <title>Abstract</title> <sec id="hel12001-sec-0001" sec-type="section"> <title>Background</title> <p> <italic>Helicobacter pylori</italic> 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 <italic>H. pylori</italic>‐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 <italic>H. pylori</italic> 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 <italic>H. pylori</italic>‐mediated gastric pathologies.</p> </sec> <sec id="hel12001-sec-0002" sec-type="section"> <title>Materials and Methods</title> <p>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.</p> </sec> <sec id="hel12001-sec-0003" sec-type="section"> <title>Results</title> <p>Homozygous 602S allele carriers exhibited impaired in vitro IFN‐γ responses to the TLR2/1 agonist Pam<sub>3</sub>CSK<sub>4</sub>. The TLR1 I602S SNP is significantly associated with GC (<italic>p</italic> = .002) and gastric ulcer (<italic>p</italic> = .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.</p> </sec> <sec id="hel12001-sec-0004" sec-type="section"> <title>Conclusion</title> <p>In conclusion, our results suggest that the nonfunctional TLR1 602S/S genotype is associated with a reduced risk of <italic>H. pylori</italic>‐induced gastric diseases, probably via diminished Th1 responses.</p> </sec> </abstract>