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.
Helicobacter
; 18(1): 13-21, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23067142
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 ANDMETHODS:
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 Pam(3) CSK(4). 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Linfócitos T
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Helicobacter pylori
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Infecções por Helicobacter
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Interferon gama
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Polimorfismo de Nucleotídeo Único
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Receptor 1 Toll-Like
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article