title: Breed-independent toll-like receptor 5 polymorphisms show association with canine inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is thought to be the most common cause of vomiting and diarrhoea in dogs. Although IBD can occur in any canine breed, certain breeds are more susceptible. We have previously shown that polymorphisms in the TLR4 and TLR5 (toll-like receptor) genes are significantly associated with IBD in German Shepherd dogs (GSDs). In order to allow for the development of novel diagnostics and therapeutics suitable for all dogs suffering from IBD, it would be useful to determine if the described polymorphisms are also significantly associated with IBD in other breeds. Therefore, the aim of this study was to investigate whether polymorphisms in the canine TLR4 and TLR5 genes are associated with IBD in other non-GSD canine breeds. The significance of the previously identified non-synonymous single nucleotide polymorphisms (SNPs) in the TLR4 (T23C, G1039A, A1571T and G1807A) and TLR5 genes (G22A, C100T and T1844C) were evaluated in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 85 unrelated dogs with IBD consisting of 38 different breeds was compared with a breed-matched control group consisting of 162 unrelated dogs. Indeed, as in the GSD IBD population, the two TLR5 SNPs (C100T and T1844C) were found to be significantly protective for IBD in other breeds (P = 0.023 and P = 0.0195 respectively). Our study suggests that the two TLR5 SNPs, C100T and T1844C could play a role in canine IBD as these were found to be protective factors for this disease in 38 different canine breeds. Thus, targeting TLR5 in the canine system may represent a suitable way to develop new treatment for IBD in dogs.
authors.affiliation: Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Kathrani
authors.forename: A
authors.initials: A
authors.lastname: House
authors.forename: B
authors.initials: B
authors.lastname: Catchpole
authors.forename: A
authors.initials: A
authors.lastname: Murphy
authors.forename: D
authors.initials: D
authors.lastname: Werling
authors.forename: K
authors.initials: K
authors.lastname: Allenspach
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004247:DNA / Q000378:metabolism; D004285:Dogs; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D013045:Species Specificity; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051198:Toll-Like Receptor 5 / Q000235:genetics*
chemical_list: D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D004247:DNA