Canine diabetes mellitus: from phenotype to genotype

Authors

  • B. Catchpole,

    1. Department of Pathology & Infectious Diseases, Royal Veterinary College, University of London, London AL9 7TA
      *Centre for Integrated Genomic Medical Research, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT
      †Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES
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  • L. J. Kennedy,

    1. Department of Pathology & Infectious Diseases, Royal Veterinary College, University of London, London AL9 7TA
      *Centre for Integrated Genomic Medical Research, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT
      †Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES
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  • L. J. Davison,

    1. Department of Pathology & Infectious Diseases, Royal Veterinary College, University of London, London AL9 7TA
      *Centre for Integrated Genomic Medical Research, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT
      †Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES
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  • W. E. R. Ollier

    1. Department of Pathology & Infectious Diseases, Royal Veterinary College, University of London, London AL9 7TA
      *Centre for Integrated Genomic Medical Research, Faculty of Medical and Human Sciences, University of Manchester, Manchester M13 9PT
      †Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES
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Abstract

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Breed differences in susceptibility to diabetes mellitus in dogs suggest an underlying genetic component to the pathogenesis of the disease. There is little evidence for an equivalent of human type 2 diabetes in dogs, and it has been proposed that canine diabetes is more comparable to the type 1 form of the disease. Certain immune response genes, particularly those encoding major histocompatibility complex molecules involved in antigen presentation, are important in determining susceptibility to human type 1 diabetes. We tested the hypothesis that canine major histocompatibility complex genes (known as the dog leucocyte antigen) are associated with diabetes in dogs. A total of 530 diabetic dogs and more than 1000 controls were typed for dog leucocyte antigen, and associations were found with three specific haplotypes. The DLA-DRB1*009/DQA1*001/DQB1*008 haplotype shows the strongest association with diabetes in the UK dog population. This haplotype is common in diabetes-prone breeds (Samoyed, cairn terrier and Tibetan terrier) but rare in diabetes-resistant breeds (boxer, German shepherd dog and golden retriever), which could explain differences in the prevalence of diabetes in these different breeds. There is evidence that the DLA-DQA1*001 allele is also associated with hypothyroidism, suggesting that this could represent a common susceptibility allele for canine immune-mediated endocrinopathies.

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