Cytochrome P450 (CYP) enzymes form an ancient and highly conserved family of oxidative enzymes that play a critical role in the metabolism and elimination of many clinically used drugs. In humans, polymorphisms in CYP2D6 are well known to influence the efficacy and conversion rate of antidepressants and other psychoactive medications.
In dogs, the orthologous enzyme CYP2D15 is of particular interest because antidepressants are commonly prescribed in veterinary behavioral medicine, yet treatment outcomes vary substantially between individuals. Until recently, detailed genetic analysis of this enzyme was limited by an incomplete and inaccurately assembled reference sequence in the CanFam3.1 genome.
To address this limitation, the authors elucidated the complete exon–intron structure of the canine CYP2D15 gene, enabling comprehensive genotyping using genomic DNA. This structural clarification provides a reliable foundation for identifying functional genetic variation across dog populations.
The study surveyed CYP2D15 sequence variation in four genetically diverse dog breeds. While most regions were conserved, the authors identified novel polymorphisms in exon 2 that were specific to Border Collies. These findings demonstrate previously unrecognized genetic diversity in a key drug-metabolizing enzyme.
Although functional consequences were not directly tested, the newly identified variants open the door for future research into how CYP2D15 polymorphisms affect enzyme expression and activity. Such variation may help explain why some dogs respond well to antidepressant therapy while others show limited efficacy or adverse effects.
The authors conclude that advancing knowledge of canine pharmacogenetics will support more individualized and effective treatment strategies, particularly in behavioral medicine where psychopharmaceuticals are frequently used and therapeutic response is highly variable.
Source: van Hagen, M. A. V., Schipper, L., Oosterveer-van der Doelen, M. A. M., Vos-Loohuis, M., Gehring, R., Leegwater, P. (2020). Analysis of polymorphisms of canine Cytochrome P450-CYP2D15. Journal of Veterinary Pharmacology and Therapeutics.
