OMIA:002421-9615 : Drug metabolism, altered in Canis lupus familiaris (dog)

In other species: domestic cat , pig , sheep

Categories: Homeostasis / metabolism phene

Single-gene trait/disorder: unknown

Disease-related: unknown

Species-specific description: Martinez et al. (2024): "Greyhounds metabolize cytochrome P450 (CYP) 2B11 substrates more slowly than other dog breeds."

Molecular basis: Martinez et al. (2020) investigatd suspected CYP2B11 deficiency in Greyhounds: "Greyhound livers metabolized CYP2B11 substrates slower, possessed lower CYP2B11 protein abundance, but had similar or higher mRNA expression than other breeds. Gene resequencing identified three CYP2B11 haplotypes, H1 (reference), H2, and H3 that were differentiated by mutations in the gene 3'-untranslated region (3'-UTR). ... Greyhounds had the highest CYP2B11-H3 allele frequency, while CYP2B11-H2 was widely distributed across most breeds. Using 3'-UTR luciferase reporter constructs, CYP2B11-H3 showed markedly lower gene expression (over 70%) compared to CYP2B11-H1 while CYP2B11-H2 expression was intermediate. Truncated mRNA transcripts were observed in CYP2B11-H2 and CYP2B11-H3 but not CYP2B11-H1 transfected cells. Our results implicate CYP2B11 3'-UTR mutations as a cause of decreased CYP2B11 enzyme expression in Greyhounds through reduced translational efficiency."
Martinez et al. (2024) identified two POR protein variants (Glu315Gln and Asp570Glu). Their "results indicate that the Glu315Gln mutation ... reduces CYP2B11 enzyme function without affecting at least one other major canine hepatic P450 (CYP2D15). Additional in vivo studies are warranted to confirm these findings."

Breed: Greyhound (Dog) (VBO_0200638).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated genes:

Symbol Description Species Chr Location OMIA gene details page Other Links
POR cytochrome p450 oxidoreductase Canis lupus familiaris 6 NC_051810.1 (7068561..7137106) POR Homologene, Ensembl , NCBI gene
CYP2B6 cytochrome P450 2B11 Canis lupus familiaris 1 NC_051805.1 (113415892..113431675) CYP2B6 Homologene, Ensembl , NCBI gene

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:002421-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

References

Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 Martinez, S.E., Pandey, A.V., Perez Jimenez, T.E., Zhu, Z., Court, M.H. :
Pharmacogenomics of poor drug metabolism in greyhounds: Canine P450 oxidoreductase genetic variation, breed heterogeneity, and functional characterization. PLoS One 19:e0297191, 2024. Pubmed reference: 38300925. DOI: 10.1371/journal.pone.0297191.
Uno, Y., Shimizu, M., Yamazaki, H. :
A variety of cytochrome P450 enzymes and flavin-containing monooxygenases in dogs and pigs commonly used as preclinical animal models. Biochem Pharmacol 228:116124, 2024. Pubmed reference: 38490520. DOI: 10.1016/j.bcp.2024.116124.
Vaidhya, A., Ghildiyal, K., Rajawat, D., Nayak, S.S., Parida, S., Panigrahi, M. :
Relevance of pharmacogenetics and pharmacogenomics in veterinary clinical practice: A review. Anim Genet 55:3-19, 2024. Pubmed reference: 37990577. DOI: 10.1111/age.13376.
2020 Martinez, S.E., Andresen, M.C., Zhu, Z., Papageorgiou, I., Court, M.H. :
Pharmacogenomics of poor drug metabolism in Greyhounds: Cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization. Sci Rep 10:69, 2020. Pubmed reference: 31919457. DOI: 10.1038/s41598-019-56660-z.
2019 Martinez, S.E., Shi, J., Zhu, H.J., Perez Jimenez, T.E., Zhu, Z., Court, M.H. :
Absolute quantitation of drug-metabolizing cytochrome P450 enzymes and accessory proteins in dog liver microsomes using label-free standard-free analysis reveals interbreed variability. Drug Metab Dispos 47:1314-1324, 2019. Pubmed reference: 31427433. DOI: 10.1124/dmd.119.088070.

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  • Created by Imke Tammen2 on 07 Sep 2024
  • Changed by Imke Tammen2 on 07 Sep 2024