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

Achyut, Bhagelu R.; Ghoshal, Uday C; Moorchung, Nikhil; Mittal, Balraj

doi:10.1016/j.humimm.2007.10.006

Cited by 79 publications

(71 citation statements)

References 39 publications

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“…Firstly, the very low allele frequency of these polymorphisms in the studied population. According to previous reports there is absence of TLR4 Asp299Gly homozygotes in Indian population and very low frequency of Thr399Ile homozygotes (0.5%) [22]. Similar result was observed in northern Indian population where the prevalence of each polymorphism was found to be 0.7% [10] [20] [23].…”

Section: Discussionsupporting

confidence: 77%

Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Dey¹,

Ghoshal²,

Agarwal³

et al. 2016

JBM

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Toll-like receptors (TLRs) 2 and 4 specifically recognize lipopolysaccharide motifs on surfaces of microorganisms. Polymorphims in the TLR genes result in structural variations in the proteins, abnormal host-pathogen interactions and hence, altered immune response. Opportunistic parasite Cryptosporidium spp. infects immunocompromised patients who present with heterogeneous clinical manifestations ranging from mild infection resolving in a few weeks, to severe form characterized by voluminous diarrhoea, prolonged symptoms and recurrences. The present study investigates the role of TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms in pathogenesis of cryptosporidiosis. Stool samples were collected from 210 immuno-compromised (renal transplant recipients and patients with Human immunodeficiency virus infection) both with and without cryptosporidiosis, and 200 healthy subjects for detection of Cryptosporidium spp. Blood samples were also collected from the patients and healthy subjects for genotyping of Δ22 (TLR2 196_174del) polymorphism, A896G (TLR4 Asp299Gly) and C1196T (Thr399Ile) single nucleotide polymorphisms (SNPs) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Cryptosporidium spp. was detected in 70 immunocompromised patients, while it was absent in all the healthy controls. No significant difference was observed in Δ22, A896G and C1196T alleles and genotypes (P > 0.05), between cases and controls. Thus, TLR2 196_174del, TLR4 Asp299Gly and Thr399Ile polymorphisms are not significantly associated with the pathogenesis or progression of cryptosporidiosis, in the Indian population included in the study.

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Section: Discussionsupporting

confidence: 77%

Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Dey¹,

Ghoshal²,

Agarwal³

et al. 2016

JBM

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“…Previously TLR4 ϩ896G carriers were shown to have an 11-fold (95% CI ϭ 2.5 to 48) increased OR of developing gastric cancer (18). The association of the TLR4 ϩ896G polymorphism and also the TLR4 ϩ1196T polymorphism with increased risk of gastric cancer have subsequently been assessed in several studies, although their prevalence is known to vary dramatically depending on the ethnic background (1,32,38,41).…”

Section: Discussionmentioning

confidence: 99%

Increase in NF-κB Binding Affinity of the Variant C Allele of the Toll-Like Receptor 9 −1237T/C Polymorphism Is Associated with Helicobacter pylori -Induced Gastric Disease

Hof

Crockett

et al. 2010

Infect Immun

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Colonization of the gastric mucosa by Helicobacter pylori can lead to serious clinical outcomes, including gastric cancer. Toll-like receptors (TLRs) play an important role in the host response to H. pylori through the recognition of pathogen-associated molecular patterns. TLR9, in particular, is partly responsible for initiating bacterial induced immunity by binding unmethylated CpG-DNA, which is abundant in bacteria. A welldocumented single nucleotide polymorphism (SNP) within the TLR9 promoter (TLR9 ؊1237T/C), is associated with a variety of inflammatory disorders, including allergic asthma, inflammatory bowel disease, and atopy. Analysis of the TLR9 promoter gene sequence has shown that carriage of the variant "C" allele at position ؊1237 creates a potential NF-B binding site that would theoretically increase the transcriptional activity of the gene. In this study, we report that the TLR9 ؊1237 C allele was significantly associated with the development of H. pylori-induced premalignant gastric changes. Functional analysis of the SNP, supporting the data generated from the genetic association study, showed that carriage of the C allele increased TLR9 transcriptional activity driven mainly by activation of NF-B. Collectively, these findings confirm that the TLR9 ؊1237T/C polymorphism is a risk factor for the development of H. pylori-induced premalignant gastric changes and provide a plausible mechanistic explanation.

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“…TLR2 and TLR4 have been shown to be important for recognition of H. pylori in neutrophils, resulting in production of IL-8 and IL-10 [55] . The TLR4 variant Asp299Gly was found to be present at similar rates in patients with a risk of gastritis and healthy controls [56] . However, the TLR4 variant Thr399Ile was detected at an increased rate in patients, and carriers had an increased level of plasma cell infiltration and development of precancerous lesions [56] .…”

Section: Gastritis Gastric Cancer and Prostate Cancermentioning

confidence: 88%

“…The TLR4 variant Asp299Gly was found to be present at similar rates in patients with a risk of gastritis and healthy controls [56] . However, the TLR4 variant Thr399Ile was detected at an increased rate in patients, and carriers had an increased level of plasma cell infiltration and development of precancerous lesions [56] . Thus, TLR4 Thr399Ile plays a possible role in the development of gastritis and gastric cancer.…”

Section: Gastritis Gastric Cancer and Prostate Cancermentioning

confidence: 88%

Genetic Variation in Toll-Like Receptor Signalling and the Risk of Inflammatory and Immune Diseases

Corr

O’Neill²

2009

J Innate Immun

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There has been growing interest in the role of host genetic factors in humans and susceptibility to infectious and inflammatory diseases. Genetic variation in Toll-like receptors (TLRs), key innate immune receptors or their signalling molecules, have been described. Variation in certain TLRs has been linked to disease susceptibility. This genetic variation can result in an altered immune response to pathogenic challenge as well as exorbitant immune activation and inflammation, and thus may influence the pathogenesis or outcome of disease. Examples include variants of TLR4 in sepsis, malaria, inflammatory bowel disease and atherosclerosis; variants in TLR2 in tuberculosis and asthma; a variant in Mal (a key signal for TLR2 and TLR4) in malaria, tuberculosis and systemic lupus erythematosus; and variants in the kinase IRAK4 in pyogenic infections. These associations provide us with a validation for the role of TLRs in human disease, and also suggest possible strategies to limit or boost TLR function in the effort to develop new therapies.

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

Cited by 79 publications

References 39 publications

Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Association between Toll-Like Receptor 4 (Thr399Ile and Asp299Gly), Toll-Like Receptor 2 196-174 Deletion Polymorphisms with cryptosporidiosis

Increase in NF-κB Binding Affinity of the Variant C Allele of the Toll-Like Receptor 9 −1237T/C Polymorphism Is Associated with Helicobacter pylori -Induced Gastric Disease

Genetic Variation in Toll-Like Receptor Signalling and the Risk of Inflammatory and Immune Diseases

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