Dilated cardiomyopathy: the same risk factors in Dobermans and humans

A study reveals that the genes responsible for this heart disease in humans and Doberman Pinschers are similar. Thus, the canine genome shares more similarities with the human genome than with that of rodents, which are typically used to model dilated cardiomyopathy. The Doberman therefore appears to be a relevant animal model for preclinical studies in humans.   A total of 540 European Dobermanns, both healthy and affected, were included in this study aimed at characterizing the genetic factors and underlying pathophysiological mechanisms that contribute to the development of dilated cardiomyopathy. The researchers identified the genetic basis of this disease, which causes heart failure due to systolic dysfunction and left ventricular dilation in both dogs and humans. New loci and candidate genes were mapped and compared across the two species. Two closely located genomics loci appear to be responsible for cardiac muscle dysfunction (both structural and metabolic). This is a significant finding, given that dilated cardiomyopathy is strongly linked to a genetic origin. More than a hundred risk genes have already been identified in humans, but not yet in Dobermans, even though the breed is genetically predisposed to this disease. Beyond the identification of two new common genetic risk factors (the RNF207 and PRKAA2 genes), it appears that they are involved only in the context of heart dilation and impaired cardiac function. As a result, arrhythmia does indeed appear to be a genetically distinct condition. A link to humans has been established: about fifteen variants potentially responsible for the disease and originating from the same two genes were studied, making the Doberman an interesting comparative model for research in humans. The medical significance of these research findings lies in understanding the mechanisms leading to cardiac dysfunction. One of the genes is involved in heart muscle contraction; its variant causes heart disease. As for the second gene, its mutation affects energy uptake in the muscle, thereby reducing its efficiency. This study has the merit of opening up new avenues of research in both veterinary medicine and human medicine. The development of a two-marker genetic test could facilitate early diagnosis of the disease in Dobermans and provide a better understanding of genetic inheritance in the context of canine breeding. Such a genetic test could play a role in both prevention and pedigree dog breeding strategies by excluding at-risk individuals from breeding. In the future, the comprehensive “One Health” approach should also lead to a better understanding of the pathophysiology of dilated cardiomyopathy in humans and potentially to the development of appropriate medications.   https://vetitude.fr/medecine-canine-cardiomyopathie-dobermann-veterinaire/