Readressing the Role of Toll-Like Receptor-4 Alleles in Inflammatory Bowel Disease: Colitis, Smoking, and Seroreactivity

Manolakis, Anastassios C.; Kapsoritakis, Andreas; Kapsoritaki, Anastasia I; Tiaka, Elisavet K.; Oikonomou, Konstantinos; Lotis, V. D.; Vamvakopoulou, Dimitra; Davidi, Ioanna P; Vamvakopoulos, Nicholas C.; Potamianos, Spyros

doi:10.1007/s10620-012-2348-4

Cited by 10 publications

(7 citation statements)

References 50 publications

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“…While an association with the surgical (but not the medical) treatment was detected in our UC patients, a correlation with the early onset of the disease has been reported in the other Tunisian study . A phenotypic association with UC pancolitis and involvement of the colon in CD was described in a Greek population . The genetic variation of TLR4 , which affects the extracellular domains of the molecule and leads to a truncated receptor, seems to induce an inappropriate innate immune response to intestinal flora (lipopolysaccharide hyporesponsiveness), which may trigger intestinal inflammation and IBD development.…”

Section: Discussionsupporting

confidence: 50%

“…20 A phenotypic association with UC pancolitis and involvement of the colon in CD was described in a Greek population. 21 The genetic variation of TLR4, which affects the extracellular domains of the molecule and leads to a truncated receptor, seems to induce an inappropriate innate immune response to intestinal flora (lipopolysaccharide hyporesponsiveness), which may trigger intestinal inflammation and IBD development.…”

Section: Discussionmentioning

confidence: 99%

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Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease

Feki

Bouzid

Abida

et al. 2017

J of Digest Diseases

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease

Feki

Bouzid

Abida

et al. 2017

J of Digest Diseases

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“…The search of PubMed, Biosis Previews, Embase and two Chinese databases (Chinese National Knowledge Infrastructure and Wanfang databases) for relevant articles published up to July 2014 yielded 597 articles. A total of 36 articles[ 23 – 58 ][ 23 – 58 ] met the inclusion criteria and were selected. Three article contained 2 separated studies each, as each of them involved two different populations.…”

Section: Resultsmentioning

confidence: 99%

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

et al. 2015

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BackgroundThe associations between toll-like receptor 2 (TLR2) and toll-like receptor 4(TLR4) polymorphisms and inflammatory bowel disease (IBD) susceptibility remain controversial. A meta-analysis was performed to assess these associations.MethodsA systematic search was performed to identify all relevant studies relating TLR2 and TLR4 polymorphisms and IBD susceptibility. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by ethnicity and publication quality.ResultsThirty-eight eligible studies, assessing 10970 cases and 7061 controls were included. No TLR2 Arg677Trp polymorphism was found. No significant association was observed between TLR2 Arg753Gln polymorphism and Crohn’s disease (CD) or ulcerative colitis (UC) in all genetic models. Interestingly, TLR4 Asp299Gly polymorphism was significantly associated with increased risk of CD and UC in all genetic models, except for the additive one in CD. In addition, a statistically significant association between TLR4 Asp299Gly polymorphism and IBD was observed among high quality studies evaluating Caucasians, but not Asians. Associations between TLR4 Thr399Ile polymorphisms and CD risk were found only in the allele and dominant models. The TLR4 Thr399Ile polymorphism was associated with UC risk in pooled results as well as subgroup analysis of high quality publications assessing Caucasians, in allele and dominant models.ConclusionsThe meta-analysis provides evidence that TLR2 Arg753Gln is not associated with CD and UC susceptibility in Asians; TLR4 Asp299Gly is associated with CD and UC susceptibility in Caucasians, but not Asians. TLR4 Thr399Ile may be associated with IBD susceptibility in Caucasians only. Additional well-powered studies of Asp299Gly and other TLR4 variants are warranted.

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“…TLR4 was linked to an increased IBD (CD or UC) risk in many other diverse investigations. Significant associations were found in patients drawn from Belgian [ 32 ], German [ 22 , 33 ], Greek [ 36 , 46 ] and Dutch [ 34 ] populations. In addition, several meta-analyses provided evidence that the Asp299Gly SNP is associated with CD and IBD in Caucasians [ 27 , 42 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms: New data and a meta-analysis

et al. 2014

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BackgroundThe pathogenesis of inflammatory bowel disease (IBD) involves interactions between the host genetic susceptibility, intestinal microflora and mucosal immune responses through the pattern recognition receptor. Polymorphisms in toll-like receptor 4 (TLR4) induce an aberrant immune response to indigenous intestinal flora, which might favor IBD development. In this study, we aimed to determine whether TLR4 gene was associated with Crohn’s disease (CD) and ulcerative colitis (UC) among Moroccan patients, and evaluated its correlation with clinical manifestation of the disease.MethodsThe study population comprised 117 patients with IBD and 112 healthy unrelated blood donors. TLR4 polymorphisms: Asp299Gly and Thr399Ile were genotyped by polymerase chain reaction-restriction fragment length polymorphism. PCR products were cleaved with Nco I for the Asp299Gly polymorphism and Hinf I for the Thr399Ile polymorphism. Meta-analysis was performed to test the association of 299Gly and 399Ileu carriage with CD, UC and the overall IBD risk.ResultsOur study revealed that the frequency of Asp299Gly and Thr399Ile did not differ significantly between patients and controls in the Moroccan population. However, meta-analysis demonstrated significantly higher frequencies of both Asp299Gly and Thr399Ile SNPs in IBD and CD and for 399Ileu carriage in UC patients.ConclusionThe meta-analysis provides evidence that TLR4 polymorphisms confer a significant increased risk for the overall IBD development.

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Readressing the Role of Toll-Like Receptor-4 Alleles in Inflammatory Bowel Disease: Colitis, Smoking, and Seroreactivity

Abstract: The presence of TLR-4 Asp299Gly and TLR-4 Thr399Ile polymorphisms is related to UC pancolitis, involvement of the colon in CD, and lower ACCA IgA levels. Smoking reduces the extent of UC, even in the presence of mutant alleles.

Cited by 10 publications

References 50 publications

Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease

Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease

Association between TLR2 and TLR4 Gene Polymorphisms and the Susceptibility to Inflammatory Bowel Disease: A Meta-Analysis

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms: New data and a meta-analysis

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