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Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions.
Hum Immunol 2007; 68(11):901-7HI

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.

Authors+Show Affiliations

Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18082569

Citation

Achyut, B R., et al. "Association of Toll-like Receptor-4 (Asp299Gly and Thr399Ileu) Gene Polymorphisms With Gastritis and Precancerous Lesions." Human Immunology, vol. 68, no. 11, 2007, pp. 901-7.
Achyut BR, Ghoshal UC, Moorchung N, et al. Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. Hum Immunol. 2007;68(11):901-7.
Achyut, B. R., Ghoshal, U. C., Moorchung, N., & Mittal, B. (2007). Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. Human Immunology, 68(11), pp. 901-7.
Achyut BR, et al. Association of Toll-like Receptor-4 (Asp299Gly and Thr399Ileu) Gene Polymorphisms With Gastritis and Precancerous Lesions. Hum Immunol. 2007;68(11):901-7. PubMed PMID: 18082569.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. AU - Achyut,B R, AU - Ghoshal,Uday C, AU - Moorchung,Nikhil, AU - Mittal,Balraj, Y1 - 2007/11/05/ PY - 2007/07/01/received PY - 2007/09/20/revised PY - 2007/10/05/accepted PY - 2007/12/18/pubmed PY - 2008/2/28/medline PY - 2007/12/18/entrez SP - 901 EP - 7 JF - Human immunology JO - Hum. Immunol. VL - 68 IS - 11 N2 - 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. SN - 0198-8859 UR - https://www.unboundmedicine.com/medline/citation/18082569/Association_of_Toll_like_receptor_4__Asp299Gly_and_Thr399Ileu__gene_polymorphisms_with_gastritis_and_precancerous_lesions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0198-8859(07)00458-2 DB - PRIME DP - Unbound Medicine ER -