Abstract
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 language | English (US) |
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Pages (from-to) | 901-7 |
Number of pages | 7 |
Journal | Human Immunology |
Volume | 68 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2007 |
Externally published | Yes |
Keywords
- 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