Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Dec 23;5(12):e15740.
doi: 10.1371/journal.pone.0015740.

Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German shepherd dogs

Aarti Kathrani  1 , Arthur House, Brian Catchpole, Angela Murphy, Alex German, Dirk Werling, Karin Allenspach
Affiliations

Polymorphisms in the TLR4 and TLR5 gene are significantly associated with inflammatory bowel disease in German shepherd dogs

Aarti Kathrani et al. PLoS One. .

Abstract

Inflammatory bowel disease (IBD) is considered to be the most common cause of vomiting and diarrhoea in dogs, and the German shepherd dog (GSD) is particularly susceptible. The exact aetiology of IBD is unknown, however associations have been identified between specific single-nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) and human IBD. However, to date, no genetic studies have been undertaken in canine IBD. The aim of this study was to investigate whether polymorphisms in canine TLR 2, 4 and 5 genes are associated with IBD in GSDs. Mutational analysis of TLR2, TLR4 and TLR5 was performed in 10 unrelated GSDs with IBD. Four non-synonymous SNPs (T23C, G1039A, A1571T and G1807A) were identified in the TLR4 gene, and three non-synonymous SNPs (G22A, C100T and T1844C) were identified in the TLR5 gene. The non-synonymous SNPs identified in TLR4 and TLR5 were evaluated further in a case-control study using a SNaPSHOT multiplex reaction. Sequencing information from 55 unrelated GSDs with IBD were compared to a control group consisting of 61 unrelated GSDs. The G22A SNP in TLR5 was significantly associated with IBD in GSDs, whereas the remaining two SNPs were found to be significantly protective for IBD. Furthermore, the two SNPs in TLR4 (A1571T and G1807A) were in complete linkage disequilibrium, and were also significantly associated with IBD. The TLR5 risk haplotype (ACC) without the two associated TLR4 SNP alleles was significantly associated with IBD, however the presence of the two TLR4 SNP risk alleles without the TLR5 risk haplotype was not statistically associated with IBD. Our study suggests that the three TLR5 SNPs and two TLR4 SNPs; A1571T and G1807A could play a role in the pathogenesis of IBD in GSDs. Further studies are required to confirm the functional importance of these polymorphisms in the pathogenesis of this disease.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: AK's PhD is funded by Pfizer and the Biotechnology and Biological Sciences Research Council - BBSRC. In addition, a grant from PetSavers was used to also fund this research. AG's senior lectureship is funded by Royal Canin. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Linkage disequilibrium of single nucleotide polymorphisms in canine TLR4.
Linkage disequilibrium plot of the four non-synonymous TLR4 single nucleotide polymorphisms in the German shepherd dog (GSD) population obtained from a case-control association study of inflammatory bowel disease. Sequencing information was obtained using a SNaPSHOT multiplex reaction (case = 55 unrelated GSDs, control = 61 GSDs).
Figure 2
Figure 2. Linkage disequilibrium of single nucleotide polymorphisms in canine TLR5.
Linkage disequilibrium plot of the three non-synonymous TLR5 SNPs in the German shepherd dog (GSD) population obtained from a case-control association study of inflammatory bowel disease. Sequencing information was obtained using a SNaPSHOT multiplex reaction (case = 55 unrelated GSDs, control = 61 GSDs).
See this image and copyright information in PMC

References

    1. Abreu MT, Fukata M, Arditi M. TLR signaling in the gut in health and disease. J Immunol. 2005;174:4453–4460. - PubMed
    1. Magalhaes JG, Tattoli I, Girardin SE. The intestinal epithelial barrier: how to distinguish between the microbial flora and pathogens. Semin Immunol. 2007;19:106–115. - PubMed
    1. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, Edberg S, Medzhitov R. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229–241. - PubMed
    1. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801. - PubMed
    1. Guilford WG. Strombecks Small Animal Gastroenterology; 1996. Idiopathic Inflammatory Bowel disease. pp. 451–486.

Publication types