Detection of the CYP1A2 1117C &gt; T polymorphism in 14 dog breeds

Aretz, Julia; Geyer, Joachim

doi:10.1111/j.1365-2885.2010.01222.x

Cited by 12 publications

(8 citation statements)

References 11 publications

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“…The Irish Wolfhound had the highest allele frequency (42%) followed by the Japanese Beagles (37–39%) and Berger Blanc Suisse (28%). Interestingly the beagles studied in Germany 25 and the USA 24 had less than half the allele frequency (15% and 13%, respectively) than the beagles from Japan 12, 13 possibly reflecting colony founder effect differences. The remaining breeds studied had allele frequencies of 10% or less indicating that the likely frequency of the enzyme deficient homozygous variant dogs would be 1% or less in the population (i.e.…”

Section: Canine Cyps With Known Genetic Polymorphismmentioning

confidence: 92%

“…Apart from research colony Beagle dogs in Japan 12, 13 , several other studies have surveyed this mutation in nearly 40 different dog breeds (and mixed breed dogs) from the USA 24 , Germany 25 , and Brazil 14 (see Figure 3). The Irish Wolfhound had the highest allele frequency (42%) followed by the Japanese Beagles (37–39%) and Berger Blanc Suisse (28%).…”

Section: Canine Cyps With Known Genetic Polymorphismmentioning

confidence: 99%

“…relatively rare). Interestingly many of the remaining affected breeds were herding dogs including Australian Shepherd, Collie, Shetland Sheepdog, Bearded Collie, Border Collie, and Old English Sheepdog 25 . Although this could be sampling bias, it might also indicate a common (although perhaps more recent) ancestry of CYP1A2stop with the MDR1 gene deletion (MDR1del) mutation, which is commonly found in herding breed dogs 26 .…”

Section: Canine Cyps With Known Genetic Polymorphismmentioning

confidence: 99%

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Canine Cytochrome P-450 Pharmacogenetics

Court

2013

Veterinary Clinics of North America: Small Animal Practice

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Synopsis The cytochrome P450 (CYP) drug metabolizing enzymes are essential for the efficient elimination of many clinically used drugs. These enzymes typically display high interindividual variability in expression and function resulting from enzyme induction, inhibition, and genetic polymorphism thereby predisposing patients to adverse drug reactions or therapeutic failure. There are also substantial species differences in CYP substrate specificity and expression that complicate direct extrapolation of information from humans to veterinary species. This article reviews the available published data regarding the presence and impact of genetic polymorphisms on CYP-dependent drug metabolism in dogs in the context of known human-dog CYP differences. Canine CYP1A2, which metabolizes phenacetin, caffeine, and theophylline, is the most widely studied polymorphic canine CYP. A single nucleotide polymorphism resulting in a CYP1A2 premature stop codon (c.1117C>T; R383X) with a complete lack of enzyme is highly prevalent in certain dog breeds including Beagle and Irish wolfhound. This polymorphism was shown to substantially affect the pharmacokinetics of several experimental compounds in Beagles during preclinical drug development. However, the impact on the pharmacokinetics of phenacetin (a substrate specific for human CYP1A2) was quite modest probably because other canine CYPs are capable of metabolizing phenacetin. Other canine CYPs with known genetic polymorphisms include CYP2C41 (gene deletion), as well as CYP2D15, CYP2E1, and CYP3A12 (coding SNPs). However the impact of these variants on drug metabolism in vitro or on drug pharmacokinetics is unknown. Future systematic investigations are needed to comprehensively identify CYP genetic polymorphisms that are predictive of drug effects in canine patients.

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Section: Canine Cyps With Known Genetic Polymorphismmentioning

confidence: 92%

Section: Canine Cyps With Known Genetic Polymorphismmentioning

confidence: 99%

Section: Canine Cyps With Known Genetic Polymorphismmentioning

confidence: 99%

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Canine Cytochrome P-450 Pharmacogenetics

Court

2013

Veterinary Clinics of North America: Small Animal Practice

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“…Different studies have examined the frequencies of several single nucleotide substitutions of canine genes that are associated with product resistance and drug sensitivity to survey other purebred populations that might be genetically at risk [ 3 24 29 ]. Our results are concordant with those obtained by other authors who have examined other canine breeds.…”

Section: Discussionmentioning

confidence: 99%

“…Single nucleotide polymorphisms (SNPs) have been identified as deficiencies in the canine CYP1A2 gene [ 3 14 21 26 27 30 31 ]. These deficiencies have been shown to significantly alter the pharmacokinetic behaviour of two drugs and associated with large inter-individual differences in the kinetic behaviour of a third drug [ 3 31 ]. The resulting deficiency of CYP1A2 has been found to cause significant kinetic variations in AC3933, YM-64277, and a few other drugs in Beagles.…”

Section: Introductionmentioning

confidence: 99%

SNP genetic polymorphisms ofMDR-1,CYP1A2andCYPB11genes in four canine breeds upon toxicological evaluation

2015

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The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations.

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Pharmacogenetics in Veterinary Anesthesia and Analgesia

Lakritz

2024

Pharmacology in Veterinary Anesthesia and Analgesia

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Detection of the CYP1A2 1117C > T polymorphism in 14 dog breeds

Cited by 12 publications

References 11 publications

Canine Cytochrome P-450 Pharmacogenetics

Canine Cytochrome P-450 Pharmacogenetics

SNP genetic polymorphisms ofMDR-1,CYP1A2andCYPB11genes in four canine breeds upon toxicological evaluation

Pharmacogenetics in Veterinary Anesthesia and Analgesia

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