OMIA 001405-9615 : Metabolizer of a cognitive enhancer in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 124060

Mendelian trait/disorder: yes

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2004

Species-specific name: Protein deletion

Species-specific description: In the first of two papers, Mise et al. (2004; Drug Metab Dispos 32:240-5) reported a polymorphism in ability to metabolize a novel cognitive enhancer AC-3933. Tenmizu et al. (2004) reported a similar polymorphism for a novel and selective phosphodiesterase type 4 inhibitor, YM-64227. In both cases, dogs were classified as poor metabolizers (PM) or extensive metabolizers (EM).

Molecular basis: By cloning and sequencing a set of likely candidate genes (based on knowledge of the physiology of this type of metabolism) Mise et al. (2004; Pharmacogenetics 14:769-73) showed that a 1117C>T nonsense mutation in the CYP1A2 gene is associated with the poor metabolizer (PM) phenotype in relation to AC-3933. The same mutation was reported by Tenmizu et al. (2004) as being associated with the PM phenotype in relation to YM-64227.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CYP1A2 cytochrome P450, family 1, subfamily A, polypeptide 2 Canis lupus familiaris 30 NC_006612.3 (37818400..37824192) CYP1A2 Homologene, Ensembl, NCBI gene

Variants

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Beagle Metabolizer of a cognitive enhancer CYP1A2 nonsense (stop-gain) CanFam3.1 30 g.37821686 c.1117C>T p. R373* rs852922442 2004 15564884 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool

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.
2006 Tenmizu, D., Noguchi, K., Kamimura, H. :
Elucidation of the effects of the CYP1A2 deficiency polymorphism in the metabolism of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-d]pyrimidine-2-(1h)-one (YM-64227), a phosphodiesterase type 4 inhibitor, and its metabolites in dogs. Drug Metab Dispos 34:1811-6, 2006. Pubmed reference: 16882764. DOI: 10.1124/dmd.106.011213.
Tenmizu, D., Noguchi, K., Kamimura, H., Ohtani, H., Sawada, Y. :
The canine CYP1A2 deficiency polymorphism dramatically affects the pharmacokinetics of 4-cyclohexyl-1-ethyl-7-methylpyrido[2,3-D]-pyrimidine-2-(1H)-one (YM-64227), a phosphodiesterase type 4 inhibitor. Drug Metab Dispos 34:800-6, 2006. Pubmed reference: 16473917. DOI: 10.1124/dmd.105.008722.
2004 Mise, M., Hashizume, T., Matsumoto, S., Terauchi, Y., Fujii, T. :
Identification of non-functional allelic variant of CYP1A2 in dogs. Pharmacogenetics 14:769-73, 2004. Pubmed reference: 15564884.
Mise, M., Yadera, S., Matsuda, M., Hashizume, T., Matsumoto, S., Terauchi, Y., Fujii, T. :
Polymorphic expression of CYP1A2 leading to interindividual variability in metabolism of a novel benzodiazepine receptor partial inverse agonist in dogs. Drug Metab Dispos 32:240-5, 2004. Pubmed reference: 14744947. DOI: 10.1124/dmd.32.2.240.
Tenmizu, D., Endo, Y., Noguchi, K., Kamimura, H. :
Identification of the novel canine CYP1A2 1117 C > T SNP causing protein deletion. Xenobiotica 34:835-46, 2004. Pubmed reference: 15742977. DOI: 10.1080/00498250412331285436.

Edit History


  • Created by Frank Nicholas on 12 Sep 2005
  • Changed by Frank Nicholas on 28 Sep 2011
  • Changed by Frank Nicholas on 12 Dec 2011
  • Changed by Frank Nicholas on 22 Sep 2012