Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions

B R Achyut, Uday C Ghoshal, Nikhil Moorchung, Balraj Mittal

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89 Scopus citations


A Toll-like receptor-4 (TLR-4) Asp299Gly and Thr399Ileu substitution reduces responsiveness to Helicobacter pylori (H. pylori) lipopolysaccharide. CagA+ strains of H. pylori are known to be associated with gastroduodenal diseases. Therefore we aimed to evaluate association of TLR-4 substitutions and CagA seropositivity with gastritis and precancerous lesions in a northern Indian population. After upper gastrointestinal endoscopy, 130 rapid urease test (RUT)-positive patients with nonulcer dyspepsia (NUD) were included. Patients with NUD were also screened for H. pylori infection using modified Giemsa staining and anti-CagA IgG enzyme-linked immunoabsorbent assay. All patients and 200 asymptomatic control subjects were genotyped for TLR-4 substitutions using polymerase chain reaction-restriction fragment length polymorphism. We observed that frequencies of TLR-4 Asp299Gly variants were comparable between patients and control subjects, and also between positive and negative groups of precancerous lesions in patients. Frequencies of TLR-4 399Ileu allele (8% vs 3%, p = 0.008) and Asp299-Ileu399 haplotype (6.5% vs 3%, p = 0.022) were higher in patients than in control subjects at risk for gastritis (OR = 2.6 and 2.5, respectively). TLR-4 399Ileu allele carriers had higher risk for plasma cell infiltration (p = 0.023, OR = 10.6) that led to atrophy (p = 0.028, OR = 4.2) and intestinal metaplasia (p = 0.009, OR = 4.7). CagA positivity was more frequently associated with lymphoid follicle formation (p = 0.033, OR = 2.53). In conclusion TLR-4 Thr399Ileu substitution may be a risk factor for gastritis and precancerous lesions. CagA positivity may be a risk factor for lymphoid follicle development but not for other precancerous lesions in a northern Indian population.

Original languageEnglish (US)
Pages (from-to)901-7
Number of pages7
JournalHuman Immunology
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • Adult
  • Alleles
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Female
  • Gastritis
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Helicobacter Infections
  • Helicobacter pylori
  • Humans
  • India
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Precancerous Conditions
  • Stomach Neoplasms
  • Toll-Like Receptor 4
  • Journal Article
  • Research Support, Non-U.S. Gov't


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