Putative candidate genes for canine hypoadrenocorticism (Addison's disease) in multiple dog breeds

CANINE hypoadrenocorticism results from structural damage/functional defects of the adrenal cortex. In human beings, 21 hydroxylase autoantibodies are an early marker for a clinically similar condition (Addison's disease) in 80–90 per cent of patients (Betterle and others 1999, Falorni and others 1995, 1997, Laureti and others 1998), but these antibodies have not been identified in dogs. There are currently no genetic or other biomarkers for the condition in dogs, and diagnosis is based on high adrenocorticotropin (ACTH) and low cortisol levels or impaired cortisol secretory response to synthetic ACTH; however, diagnosis is complicated and often delayed because of the multifaceted clinical presentation. With a timely diagnosis, affected animals can be treated and they can live a relatively normal life, but many dogs are treated incorrectly for more common conditions, reaching ‘Addisonian crisis’ before a diagnosis has been made. Understanding the genetic involvement in canine hypoadrenocorticism could facilitate the development of a genetic test for disease risk that could be used to identify dogs at increased risk for hypoadrenocorticism and enrol them into a screening programme. Furthermore, it could be used to inform breeding strategies and reduce the incidence of hypoadrenocorticism in susceptible dog breeds. Currently, there is limited understanding of the genetic aetiology in dogs or human beings, although the human leucocyte antigen DRB1 is widely accepted as a functional susceptibility locus in the latter with further risk given by the major histocompatibility complex (MHC) class l region (Gombos and others 2007, Erichsen and others …