Analysis of Candidate Susceptibility Genes in Canine Diabetes
Canine diabetes is a complex genetic disease of unknown aetiology. It affects 0.005–1.5 % of the canine population and shows a clear breed predisposition with the Samoyed being at high risk and the Boxer being at low risk of developing the disease. Canine diabetes is considered to be a disease homol...
| Main Authors: | , , , , , , , |
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| Format: | Text |
| Language: | English |
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| Online Access: | http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.574.1640 http://jhered.oxfordjournals.org/content/98/5/518.full.pdf |
| Summary: | Canine diabetes is a complex genetic disease of unknown aetiology. It affects 0.005–1.5 % of the canine population and shows a clear breed predisposition with the Samoyed being at high risk and the Boxer being at low risk of developing the disease. Canine diabetes is considered to be a disease homologue for human type 1 diabetes (T1D). It results in insulin deficiency as a consequence of autoimmune destruction of islet b-cells in the pancreas and is believed to be mediated by Th1 cytokines (IFNc, TNFa, and IL-2). A number of genes have been associated with type 1 diabetes in humans, including the human leukocyte antigen region, the insulin variable number tandem repeat, PTPN22, CTLA4, IL-4, and IL-13. As yet, these genes have not been evaluated in canine diabetes. In this study, 483 cases of canine diabetes and 869 controls of known breed were analyzed for association with IFNc, IGF2, IL-10, IL-12b, IL-6, insulin, PTPN22, RANTES, IL-4, IL-1a and TNFa. Minor allele frequencies were determined for these genes in each breed. These data were used for comparative analyses in a case– control study, and clear associations with diabetes were identified in some breeds with certain alleles of candidate genes. Some associations were with increased susceptibility to the disease (IFNc, IL-10, IL-12b, IL-6, insulin, PTPN22, IL-4, and TNFa), whereas others were protective (IL-4, PTPN22, IL-6, insulin, IGF2, TNFa). This study demonstrates that a number of the candidate genes previously associated with human T1D also appear to be associated with canine diabetes and identifies an |
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