T cell cytokine gene polymorphisms in canine diabetes mellitus

Andrea D. Short, Brian Catchpole, Lorna J. Kennedy, Annette Barnes, Andy C. Lee, Chris A. Jones, Neale Fretwell, William E R Ollier

    Research output: Contribution to journalArticlepeer-review


    Insulin-deficiency diabetes in dogs shares some similarities with human latent autoimmune diabetes of adults (LADA). Canine diabetes is likely to have a complex pathogenesis with multiple genes contributing to overall susceptibility and/or disease progression. An association has previously been shown between canine diabetes and MHC class II genes, although other genes are also likely to contribute to the genetic risk. Potential diabetes susceptibility genes include immuno-regulatory TH1/TH2 cytokines such as IFNγ, IL-12, IL-4 and IL-10. We screened these candidate genes for single nucleotide polymorphisms (SNPs) in a range of different dog breeds using dHPLC analysis and DNA sequencing. Thirty-eight of the SNPs were genotyped in crossbreed dogs and seven other breed groups (Labrador Retriever, West Highland White Terrier, Collie, Schnauzer, Cairn Terrier, Samoyed and Cavalier King Charles Spaniel), which demonstrated substantial intra-breed differences in allele frequencies. When SNPs were examined for an association with diabetes by case:control analysis significant associations were observed for IL-4 in three breeds, the Collie, Cairn Terrier and Schnauzer and for IL-10 in the Cavalier King Charles Spaniel. These results suggest that canine cytokine genes regulating the TH1/TH2 immune balance might play a contributory role in determining susceptibility to diabetes in some breeds. © 2008 Elsevier B.V. All rights reserved.
    Original languageEnglish
    Pages (from-to)137-146
    Number of pages9
    JournalVeterinary Immunology and Immunopathology
    Issue number1-3
    Publication statusPublished - 15 Mar 2009


    • Canine diabetes
    • IFNγ
    • IL-10
    • IL-12β
    • IL-4
    • Single nucleotide polymorphism


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