title: Canine diabetes mellitus: from phenotype to genotype.
abstract: 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.
authors.affiliation: Department of Pathology and Infectious Diseases, Royal Veterinary College, University of London, London AL9 7TA, UK.
authors.forename: B
authors.initials: B
authors.lastname: Catchpole
authors.forename: L J
authors.initials: LJ
authors.lastname: Kennedy
authors.forename: L J
authors.initials: LJ
authors.lastname: Davison
authors.forename: W E R
authors.initials: WE
authors.lastname: Ollier
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D004283:Dog Diseases / Q000145:classification / Q000235:genetics* / Q000276:immunology; D004285:Dogs; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D010641:Phenotype; D012307:Risk Factors; D013045:Species Specificity
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II