PMID- 18082569 OWN - NLM STAT- MEDLINE DCOM- 20080227 LR - 20210103 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 68 IP - 11 DP - 2007 Nov TI - Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions. PG - 901-7 AB - 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. FAU - Achyut, B R AU - Achyut BR AD - Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India. FAU - Ghoshal, Uday C AU - Ghoshal UC FAU - Moorchung, Nikhil AU - Moorchung N FAU - Mittal, Balraj AU - Mittal B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071105 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (Antibodies, Bacterial) RN - 0 (Antigens, Bacterial) RN - 0 (Bacterial Proteins) RN - 0 (TLR4 protein, human) RN - 0 (Toll-Like Receptor 4) RN - 0 (cagA protein, Helicobacter pylori) SB - IM MH - Adult MH - Alleles MH - Antibodies, Bacterial/*blood MH - Antigens, Bacterial/*immunology MH - Bacterial Proteins/*immunology MH - Female MH - Gastritis/*genetics/immunology/metabolism/microbiology MH - Gene Frequency MH - Genetic Predisposition to Disease MH - Genotype MH - Helicobacter Infections/immunology/microbiology MH - Helicobacter pylori/immunology MH - Humans MH - India MH - Male MH - Middle Aged MH - *Polymorphism, Genetic MH - Polymorphism, Restriction Fragment Length MH - Precancerous Conditions/*genetics/immunology/metabolism/microbiology MH - Stomach Neoplasms/*genetics/immunology/metabolism/microbiology MH - Toll-Like Receptor 4/blood/*genetics EDAT- 2007/12/18 09:00 MHDA- 2008/02/28 09:00 CRDT- 2007/12/18 09:00 PHST- 2007/07/01 00:00 [received] PHST- 2007/09/20 00:00 [revised] PHST- 2007/10/05 00:00 [accepted] PHST- 2007/12/18 09:00 [pubmed] PHST- 2008/02/28 09:00 [medline] PHST- 2007/12/18 09:00 [entrez] AID - S0198-8859(07)00458-2 [pii] AID - 10.1016/j.humimm.2007.10.006 [doi] PST - ppublish SO - Hum Immunol. 2007 Nov;68(11):901-7. doi: 10.1016/j.humimm.2007.10.006. Epub 2007 Nov 5.