MHC class II association study in eight breeds of dog with hypoadrenocorticism.
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.
Centre for Integrated Genomic Medical Research (CIGMR), School of Medicine, University of Manchester, 2.722 Stopford Building, Oxford Road, Manchester, M13 9PT, UK. jonathan.massey@manchester.ac.uk
Jonathan
J
Massey
Alisdair
A
Boag
Andrea D
AD
Short
Rachel A
RA
Scholey
Paula S
PS
Henthorn
Meryl P
MP
Littman
Eystein
E
Husebye
Brian
B
Catchpole
Niels
N
Pedersen
Cathryn S
CS
Mellersh
William E R
WE
Ollier
Lorna J
LJ
Kennedy
D000309:Adrenal Insufficiency / Q000235:genetics / Q000662:veterinary*; D000595:Amino Acid Sequence; D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D059866:HLA-DQ beta-Chains / Q000737:chemistry / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000737:chemistry / Q000235:genetics; D006239:Haplotypes; D006720:Homozygote; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D059866:HLA-DQ beta-Chains; D059811:HLA-DRB1 Chains