Abstract
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.
Highlights
The pathogenesis of inflammatory bowel disease (IBD) involves interactions between the host genetic susceptibility, intestinal microflora and mucosal immune responses through the pattern recognition receptor
Hundred and seventeen patients with IBD (83 Crohn? s disease (CD); 34 ulcerative colitis (UC)) and 112 control subjects from the general population were genotyped for the presence of TLR4Asp299Gly and Thr399Ile polymorphisms
In view of the discrepant data regarding the association of the toll-like receptor 4 (TLR4) gene with IBD and its clinical complications, we investigated for the first time the potential influence of TLR4 SNPs in the susceptibility to IBD in a cohort of Moroccan patients
Summary
The 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. The precise etiology of IBD is unclear, several factors that play a crucial role in disease pathogenesis such as commensal bacterial flora and genes related to the host immune response have been identified [1,2]. Signal transduction through TLR4 in combination with CD14, and MD-2 leads to activation of the nuclear factor-κB (NF-κB) system through the MyD88-dependent and MyD88-independent pathways and subsequent expression of inflammatory genes encoding cytokines and cell conjugation molecules as part of host defense mechanisms [6,7,8,9]
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