Cytochrome P450 (CYP) proteins constitute a large ancient family of oxidative enzymes essential for the efficient elimination of a wide variety of clinically used drugs. Polymorphic variants of human CYP2D6 are associated with the conversion rate and efficacy of several drugs such as antidepressants. Polymorphisms of the canine orthologue CYP2D15 are of interest because these antidepressants are also used in dogs with behavioral problems and the outcome of the treatment is variable. However, the annotated CYP2D15 gene is incomplete and inaccurately assembled in CanFam3.1, hampering DNA sequence analysis of the gene in individual dogs. We elucidated the complete exon–intron structure of CYP2D15 to enable comprehensive genotyping of the gene using genomic DNA. We surveyed variations of the gene in four diverse dog breeds and identified novel polymorphisms in exon 2 in border collies. Further investigation to establish the impact of these canine CYP2D15 polymorphisms on interindividual variability in expression and function of this metabolizing enzyme is now feasible. Further knowledge of CYP pharmacogenetics will help individualize therapy and thereby increase therapeutic efficacy, especially in the use of antidepressants in veterinary behavioral medicine.

中文翻译：

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犬细胞色素P 450-CYP2D15的多态性分析。

细胞色素P450（CYP）蛋白构成了一个古老的氧化酶家族，对于有效消除多种临床使用的药物而言是必不可少的。人CYP2D6的多态性变体与几种药物（例如抗抑郁药）的转化率和功效相关。犬直系同源物CYP2D15的多态性是令人感兴趣的，因为这些抗抑郁药也用于行为有问题的狗，并且治疗结果是可变的。但是，注释的CYP2D15基因在CanFam3.1中不完整且组装不准确，从而妨碍了该基因在狗中的DNA序列分析。我们阐明了CYP2D15的完整外显子-内含子结构以使用基因组DNA对基因进行全面的基因分型。我们调查了四个不同犬种中该基因的变异，并在边境牧羊犬的第2外显子中发现了新的多态性。建立这些犬CYP2D15多态性对这种代谢酶的表达和功能的个体差异的影响的进一步研究现在是可行的。CYP药物遗传学的进一步了解将有助于个体化治疗，从而提高治疗效果，尤其是在兽医学行为医学中使用抗抑郁药时。