Genetics: Canine ACE Gene Polymorphism
The classical renin-angiotensin aldosterone system (RAAS), which is the neurohormonal cascade initiated by the release of renin and ending in the stimulation of aldosterone release from the adrenal glands, is activated in dogs with advanced heart disease, and contributes to disease progression and clinical signs.
Canine ACE gene polymorphism testing: $48.00 per dog, or or $38.00 per puppy for two or more puppies of the same litter.
The major end-metabolites of the classical RAAS are angiotensin II and aldosterone, both of which directly or indirectly mediate sodium and water retention, vasoconstriction, and pathological remodeling of cardiac, vascular, and renal tissues. Angiotensin-converting enzyme (ACE)-inhibitors prevent a major step in the RAAS pathway, the conversion of angiotensin I to angiotensin II, and thereby mitigate the maladaptive effects of these neurohormones through reduced formation of angiotensin II and angiotensin-II-driven aldosterone production. Polymorphisms of the ACE gene are recognized in humans and dogs, which could influence the therapeutic strategies and outcome of diseases in which the RAAS plays a pathogenic role.
This genetic test examines one particular polymorphism that provides insight into the effectiveness of ACE-inhibitors such as Enalapril as treatment for mitral valve disease in a given dog. The magnitude of aldosterone breakthrough – the inadequate or temporary suppression of aldosterone despite administration of appropriate doses of ACE-inhibitors – is greater in dogs positive for the polymorphism. This occurs despite suppression of angiotensin II formation with Enalapril, and given that the aldosterone to angiotensin II ratio is significantly greater in polymorphism-positive dogs after Enalapril treatment, this indicates that the ACE gene polymorphism may influence a yet unidentified angiotensin II-independent pathway of aldosterone stimulation.
In conclusion, although aldosterone breakthrough occurs in a substantial minority (30-40%) of dogs receiving ACE-inhibitors, this genetic test can be a helpful tool to predict which patients will be affected. Dogs that are positive for the ACE gene polymorphism might be at greater risk for adverse effects associated with unopposed circulating aldosterone than dogs negative for the polymorphism, despite the effectiveness of Enalapril in suppressing angiotensin II. Therefore, dogs that are positive for the polymorphism may benefit the most from the administration of aldosterone receptor antagonists in conjunction with ACE-inhibitors as treatment for mitral valve disease.