Abstract
Canine hypoadrenocorticism is an endocrine disorder characterised by inadequate secretion of steroid hormones from the adrenal glands. Pathology results from immune-mediated destruction of the adrenal cortex, which is similar to that seen in the human Addison’s disease. Both the canine and human diseases have similar clinical presentation, with the diagnosis based on performing a dynamic adrenocorticotropic hormone stimulation test. MHC class II has previously been associated with the human and canine diseases. In the current study, we conducted an MHC class II association study in eight breeds of dog with diagnoses of hypoadrenocorticism. We demonstrated significant differences in dog leukocyte antigen (DLA) haplotype frequencies in six of these breeds: Cocker spaniel, Springer spaniel, Labrador, West Highland white terrier (WHWT), Bearded collie, and Standard poodle. In the Springer spaniel, the DLA-DRB1*015:01--DQA1*006:01--DQB1*023:01 haplotype was significantly associated with disease risk (p = 0.014, odds ratio (OR) = 5.14) and showed a similar trend in the Cocker spaniel. This haplotype is related to one associated with hypoadrenocorticism in the Nova Scotia duck tolling retriever. Similar haplotypes shared between breeds were demonstrated, with DLA-DRB1*001:01--DQA1*001:01--DQB1*002:01 more prevalent in both affected Labrador (p = 0.0002, OR = 3.06) and WHWT (p = 0.01, OR = 2.11). Other haplotypes that have not previously been associated with the disease were identified. The inter-breed differences in DLA haplotypes associated with susceptibility to canine hypoadrenocorticism could represent divergent aetiologies. This could have implications for clinical diagnosis and future comparative studies. Alternatively, it may suggest that the gene of interest is closely linked to the MHC.
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Acknowledgments
We would like to thank Jo Tucker (Canine Immune Mediated Disease Awareness, CIMDA) for being instrumental in encouraging sample collection. We would also like to thank IDEXX laboratories (Harrogate, UK), Nationwide Laboratories (Poulton-le-Fylde, UK), Angela Pedder, Colleen Stead, the Bearded Collie Breed Club (UK Northern Branch), Lucy Davison, Betty Aughey, all dog owners, and clinicians for submitting samples for inclusion in the study. Acknowledgments also go to the technical staff supporting the UK DNA Archive for Companion Animals, namely Steven Quarmby, Ezinne Ibe, and Simon Rothwell. This work was supported by the European Commission FP7 project number 201167, Euradrenal.
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Haplotype counts for the six breeds with significant associations (PDF 91 kb)
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Haplotype counts for the two breeds with only suggestive or no significant associations (PDF 60 kb)
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Massey, J., Boag, A., Short, A.D. et al. MHC class II association study in eight breeds of dog with hypoadrenocorticism. Immunogenetics 65, 291–297 (2013). https://doi.org/10.1007/s00251-013-0680-2
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DOI: https://doi.org/10.1007/s00251-013-0680-2