Prevalence of an angiotensin-converting enzyme gene variant in dogs

Abstract

Genetic heterogeneity of the canine angiotensin converting enzyme (ACE) gene is functionally important because the degree of aldosterone breakthrough with ACE-inhibitor therapy is greater in variant positive dogs compared to variant negative dogs, but the prevalence of the variant is not known. The purpose of this study was to determine ACE gene variant-positive prevalence in a population of 497 dogs of different breeds. Overall variant-positive prevalence was 31%, with 20% of dogs heterozygous and 11% of dogs homozygous. The variant was overrepresented in Irish Wolfhounds (prevalence 95%; P < .001), Dachshunds (prevalence 90%; P < .001), Cavalier King Charles Spaniels (prevalence 85%; P < .001), Great Danes (prevalence 84%; P < .001), and Bull Mastiffs (prevalence 58%; P = .02). Irish Wolfhounds were more likely to be homozygous than heterozygous (P < .001). Nearly one-third of dogs in this study were positive for a functionally important ACE gene variant, with wide prevalence variability between breeds. The clinical importance of high ACE gene variant-positive prevalence in some breeds requires further study because the highest prevalences were found in breeds that are predisposed to heart disease and therefore may be treated with ACE-inhibitors. Genetic differences in the angiotensin converting enzyme (ACE) have been shown to affect the way dogs respond to ACE-inhibitors, a class of medication which is used to treat dogs with heart disease. Dogs that have a genetic mutation of the ACE gene show less benefit with ACE-inhibitor medications than dogs without the mutation, but it is not known how common the mutation is in dogs. The purpose of this study was to determine the prevalence of this mutation (variant) in a large population of dogs of different breeds. The overall variant-positive prevalence in this population of 497 dogs was 31%. The variant was overrepresented in Irish Wolfhounds (prevalence 95%), Dachshunds (prevalence 90%), Cavalier King Charles Spaniels (prevalence 85%), Great Danes (prevalence 84%), and Bull Mastiffs (prevalence 58%). Irish Wolfhounds were more likely than other breeds to have 2 copies of the mutation (homozygous) than 1 copy of the mutation (heterozygous). The clinical importance of high ACE gene variant-positive prevalence in some breeds will require additional studies because some breeds are predisposed to heart disease, for which treatment with ACE-inhibitor medication might be recommended.