ArticlePloS one2013
A non-synonymous coding variant (L616F) in the TLR5 gene is potentially associated with Crohn's disease and influences responses to bacterial flagellin.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Impact of Functional Polymorphisms on Drug Survival of Biological Therapies in Patients with Moderate-to-Severe Psoriasis.International journal of molecular sciences · 2023Observational
- Play the plug: How bacteria modify recognition by host receptors?Frontiers in microbiology · 2022Article
- Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways.Computational and structural biotechnology journal · 2021Article
- Toward a porcineGut microbes · 2020Article
- Functional expression of TLR5 of different vertebrate species and diversification in intestinal pathogen recognition.Scientific reports · 2018Article
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- Associations between functional polymorphisms and response to biological treatment in Danish patients with psoriasis.The pharmacogenomics journal · 2018Article
- Toll-like Receptors and Inflammatory Bowel Disease.Frontiers in immunology · 2018Review
- Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.The pharmacogenomics journal · 2018Article
- The expression of Toll-like receptor 5 in preterm histologic chorioamnionitis.Journal of clinical biochemistry and nutrition · 2018Article
- Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis.PloS one · 2015Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
objectivesAlthough numerous studies have implicated TLR5, or its ligands, bacterial flagellins, in the pathogenesis of Crohn's disease (CD), genome-wide association studies (GWAS) have not reported associations with the TLR5 gene. We aimed to examine potential CD-associated TLR5 variants and assess whether they modified inflammatory responses to bacterial flagellins. METHODS AND PRINCIPAL
resultsA two-stage study was carried out. In stage 1, we genotyped tagging single-nucleotide polymorphisms (tag-SNPs) in the TLR5 gene in a sample of CD cases (<20 years of age, N = 566) and controls (N = 536). Single SNP and haplotype analysis was carried out. In Stage 2, we assessed the functional significance of potential CD-associated variant(s) vis-à-vis effects on the inflammatory response to bacterial flagellin using HEK293T cells. We observed marginal association between a non-synonymous coding SNP rs5744174 (p = 0.05) and CD. Associations between SNP rs851139 that is in high linkage disequilibrium (LD) with SNP rs5744174 were also suggested (p = 0.07). Haplotype analysis revealed that a 3 marker haplotype was significantly associated with CD (p = 0.01). Functional studies showed that the risk allele (616F) (corresponding to the C allele of SNP rs5744174) conferred significantly greater production of CCL20 in response to a range of flagellin doses than the comparator allele (616L).
conclusionsOur findings suggest that a non-synonymous coding variation in the TLR5 gene may confer modest susceptibility for CD.
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