Uveodermatologic (VKH-like) syndrome in American Akita dogs is associated with an increased frequency of DQA1*00201

The Akita breed of dog is affected by a number of distinct immune-mediated diseases, including thyroiditis, sebaceous adenitis, pemphigus foliaceus, uveitis, polyarthritis, myasthenia gravis, and uveodermatologic (UV) syndrome. UV syndrome is manifested by progressive uveitis and depigmenting dermatitis that closely resembles the human Vogt - Koyanagi - Harada syndrome. This study examined the allelic diversity of the three DLA class II loci (DRB1, DQA1, and DQB1) in the American Akita dog, and the relationship of specific DLA class II alleles to the UV. Low allelic variation was demonstrated within genes of DLA class II. American Akita dogs possessed six of the reported 16 DQA1 alleles, but only eight of 61 reported alleles in DRB1 and nine of 47 reported alleles in DQB1. Almost one-half of American Akita dogs were homozygous for a single allele at DQA1 and up to a quarter at DRB1 and DQB1. DLA-DQA1*00201 was associated with a significantly higher relative risk (RR = 15.3) or odds ratio (OR = 15.99) for UV syndrome than other DLA class II alleles. No significant association was noted with haplotypes of DRB1, DQB1, and DQA1 alleles; DRB1*03201-DQA1*00201 trended toward significance. This study confirmed loss of DLA genetic diversity in the American Akita dog in common with other pure breeds of dog and suggested a role for certain DLA class II gene alleles in the pathogenesis of UV.