TY - JOUR
T1 - Analysis of candidate susceptibility genes in canine diabetes
AU - Short, Andrea D.
AU - Catchpole, Brian
AU - Kennedy, Lorna J.
AU - Barnes, Annette
AU - Fretwell, Neale
AU - Jones, Chris
AU - Thomson, Wendy
AU - Ollier, William E R
N1 - DA - 20070831IS - 0022-1503 (Print)LA - engPT - Journal ArticleSB - IM
PY - 2007
Y1 - 2007
N2 - 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 β-cells in the pancreas and is believed to be mediated by Th1 cytokines (IFNγ, TNFα, 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 IFNγ, IGF2, IL-10, IL-12β, IL-6, insulin, PTPN22, RANTES, IL-4, IL-1α and TNFα. 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 (IFNγ, IL-10, IL-12β, IL-6, insulin, PTPN22, IL-4, and TNFα), whereas others were protective (IL-4, PTPN22, IL-6, insulin, IGF2, TNFα). 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 IL-10 haplotype which is associated with diabetes in the Cavalier King Charles Spaniel. This suggests that canine diabetes is an excellent comparative and spontaneously occurring disease model of human T1D. © The American Genetic Association. 2007. All rights reserved.
AB - 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 β-cells in the pancreas and is believed to be mediated by Th1 cytokines (IFNγ, TNFα, 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 IFNγ, IGF2, IL-10, IL-12β, IL-6, insulin, PTPN22, RANTES, IL-4, IL-1α and TNFα. 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 (IFNγ, IL-10, IL-12β, IL-6, insulin, PTPN22, IL-4, and TNFα), whereas others were protective (IL-4, PTPN22, IL-6, insulin, IGF2, TNFα). 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 IL-10 haplotype which is associated with diabetes in the Cavalier King Charles Spaniel. This suggests that canine diabetes is an excellent comparative and spontaneously occurring disease model of human T1D. © The American Genetic Association. 2007. All rights reserved.
KW - Alleles
KW - analysis
KW - CANINE
KW - Case-Control Studies
KW - Human
KW - Humans
KW - Risk
U2 - 10.1093/jhered/esm048
DO - 10.1093/jhered/esm048
M3 - Article
SN - 0022-1503
VL - 98
SP - 518
EP - 525
JO - Journal of Heredity
JF - Journal of Heredity
IS - 5
ER -