Kathrani A, House A, Catchpole B, Murphy A, Werling D, Allenspach K
Department of Veterinary Clinical Sciences, Royal Veterinary College, University of London, London, UK.
Tissue Antigens. 2011 Aug;78(2):94-101. doi: 10.1111/j.1399-0039.2011.01707.x. Epub 2011 May 29.
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.
炎症性肠病(IBD)被认为是犬类呕吐和腹泻的最常见原因。虽然IBD可发生于任何犬种,但某些犬种更易患病。我们之前已经表明,TLR4和TLR5(Toll样受体)基因的多态性与德国牧羊犬(GSD)的IBD显著相关。为了开发适用于所有患有IBD的犬类的新型诊断方法和治疗方法,确定所描述的多态性在其他犬种中是否也与IBD显著相关将是有用的。因此,本研究的目的是调查犬类TLR4和TLR5基因的多态性是否与其他非GSD犬种的IBD相关。在一项病例对照研究中,使用SNaPSHOT多重反应评估了TLR4(T23C、G1039A、A1571T和G1807A)和TLR5基因(G22A、C100T和T1844C)中先前鉴定的非同义单核苷酸多态性(SNP)的意义。将来自85只患有IBD的无关犬(包括38个不同品种)的测序信息与由162只无关犬组成的品种匹配对照组进行比较。事实上,与GSD的IBD群体一样,发现两个TLR5 SNP(C100T和T1844C)对其他品种的IBD具有显著的保护作用(分别为P = 0.023和P = 0.0195)。我们的研究表明,两个TLR5 SNP,即C100T和T1844C可能在犬类IBD中起作用,因为在38个不同的犬种中发现它们是这种疾病的保护因素。因此,在犬类系统中靶向TLR可能是开发犬类IBD新治疗方法的合适途径。