DNA Sequence Variants in the Carbonyl Reductase 1 Gene (cbr1) in 7 Breeds of Canis Lupus Familiaris

• Published in: Genetics and Molecular Research
• Main Authors: Cheng, Qiuying, Sanborn, Carrie, Ferguson, Daniel, Blanco, Javier G.
• Format: Text
• Language: English
• Published: 2012
• Subjects: Article; Canis lupus
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368598; http://www.ncbi.nlm.nih.gov/pubmed/22614280; https://doi.org/10.4238/2012.April.27.10

The anticancer anthracyclines doxorubicin and daunorubicin are used to treat a variety of cancers in dogs. The therapeutic utility of anthracyclines is limited by the development of cardiotoxicity in some cases. The synthesis of anthracycline alcohol metabolites by carbonyl reductase 1 (CBR1) is crucial during the pathogenesis of cardiotoxicity. We hypothesize that genetic polymorphisms in canine cbr1 may contribute to the variable pharmacodynamics of anthracyclines in dogs. This study documents DNA sequence variants in canine cbr1 by examining DNA samples from dogs from 7 breeds. Thirteen SNPs were detected in canine cbr1. A 10 bp deletion in the 5′-untranslated region (5′-UTR) was present in specimens from the Labrador Retriever, Beagle, Siberian Husky, and Boxer breeds. The 5′-UTR also included a polymorphic “hot spot region” immediately downstream the 10 bp deletion. DNA sequence variants in the “hot spot region” ranged from 1 to 21 bp in length. Bioinformatics searches identified a cluster of 3 to 6 potential binding sites for the transcription factor Sp1 in the DNA segment containing both the “hot spot region” and the 10 bp deletion. This study provides the foundation to investigate whether DNA sequence variants in the 5′-UTR of canine cbr1 impacts the pharmacodynamics of anticancer anthracyclines in dogs.