title: Association of an MHC class II haplotype with increased risk of polymyositis in Hungarian Vizsla dogs.
abstract: A breed-specific polymyositis is frequently observed in the Hungarian Vizsla. Beneficial clinical response to immunosuppressive therapies has been demonstrated which points to an immune-mediated aetiology. Canine inflammatory myopathies share clinical and histological similarities with the human immune-mediated myopathies. As MHC class II associations have been reported in the human conditions we investigated whether an MHC class II association was present in the canine myopathy seen in this breed. 212 Hungarian Vizsla pedigree dogs were stratified both on disease status and degree of relatedness to an affected dog. This generated a group of 29 cases and 183 "graded" controls: 93 unaffected dogs with a first degree affected relative, 44 unaffected dogs with a second degree affected relative, and 46 unaffected dogs with no known affected relatives. Eleven DLA class II haplotypes were identified, of which, DLA-DRB1*02001/DQA1*00401/DQB1*01303, was at significantly raised frequency in cases compared to controls (OR = 1.92, p = 0.032). When only control dogs with no family history of the disease were compared to cases, the association was further strengthened (OR = 4.08, p = 0.00011). Additionally, a single copy of the risk haplotype was sufficient to increase disease risk, with the risk substantially increasing for homozygotes. There was a trend of increasing frequency of this haplotype with degree of relatedness, indicating low disease penetrance. These findings support the hypothesis of an immune-mediated aetiology for this canine myopathy and give credibility to potentially using the Hungarian Vizsla as a genetic model for comparative studies with human myositis.
authors: Centre for Integrated Genomic Medical Research (CIGMR), Institute of Population Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, United Kingdom. jonathan.massey@manchester.ac.uk
authors: Jonathan
authors: J
authors: Massey
authors: Simon
authors: S
authors: Rothwell
authors: Clare
authors: C
authors: Rusbridge
authors: Anna
authors: A
authors: Tauro
authors: Diane
authors: D
authors: Addicott
authors: Hector
authors: H
authors: Chinoy
authors: Robert G
authors: RG
authors: Cooper
authors: William E R
authors: WE
authors: Ollier
authors: Lorna J
authors: LJ
authors: Kennedy
mesh_terms: D000818:Animals; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006720:Homozygote; D008297:Male; D017285:Polymyositis / Q000235:genetics / Q000662:veterinary*
chemical_list: D000949:Histocompatibility Antigens Class II