Prevalence of an angiotensin-converting enzyme gene variant in dogs

Abstract

Background 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. Results 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). Conclusions 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.

Influence of sex on renin‐angiotensin‐aldosterone system metabolites and enzymes in Doberman Pinschers

“…A previous study showed predispositions for the ACE variant in several breeds known to have genetically‐based heart disease (e.g., Irish Wolfhounds, Cavalier King Charles Spaniels), but there were insufficient numbers of DP in that study to assess breed predisposition 18 . Our study suggests a high prevalence of the ACE variant in DP.…”

“…The activities of ACE reported in our study are specific to the equilibrium dialysis approach and are not directly comparable to studies utilizing other methodologies. Another limitation of our study is the use of a single breed, which restricts applicability to other breeds, especially in light of breed predispositions for, and the potential influence of, the ACE variant 14,18 . Neutered male dogs also were not evaluated in our study because studies in people have indicated that estradiol is the major influencer of the RAAS and testosterone appears to have little effect on the cascade.…”

“…Another limitation of our study is the use of a single breed, which restricts applicability to other breeds, especially in light of breed predispositions for, and the potential influence of, the ACE variant. 14 , 18 Neutered male dogs also were not evaluated in our study because studies in people have indicated that estradiol is the major influencer of the RAAS and testosterone appears to have little effect on the cascade. Enrolled dogs were apparently healthy based on history, physical examination, limited ECG monitoring, and echocardiography, but screening blood tests, thyroid testing, heartworm testing, Holter monitoring, blood pressure, and urinalysis were not performed.…”

“…Residual serum from samples that were collected as part of an observational study evaluating the cardiac function of dogs eating grain‐free and grain‐inclusive diets 15 was used to evaluate core RAAS metabolites (angiotensin I, angiotensin II, angiotensin III, angiotensin IV, angiotensin 1‐7, angiotensin 1‐5, aldosterone) and the enzyme activities of ACE and ACE2. Dogs were genotyped for variants associated with dilated cardiomyopathy (DCM) in this breed, including DCM1 (pyruvate kinase dehydrogenase 4) and DCM2 (titin), 16 as well as for the known ACE gene variant 17 , 18 ( https://cvm.ncsu.edu/nc-state-vet-hospital/small-animal/genetics/submit-dna-testing/ ). Sample collection was approved by the University of Florida IACUC committee (#201810504), and client consent was obtained from owners.…”

Aldosterone-progesterone relationship in sexually intact Chihuahua bitches

“…In a previous study, Chihuahua showed significantly higher UAldo:C compared to other breeds [ 9 ]. Polymorphism of angiotensin converting enzyme has been reported in dogs, with wide prevalence variability among breeds 36 . This gene variant has been associated with higher aldosterone levels and aldosterone breakthrough incidence in dogs [ 8 ].…”