• 1.

    Fujita K, Sasaki Y. Pharmacogenomics in drug-metabolizing enzymes catalyzing anticancer drugs for personalized cancer chemotherapy. Curr Drug Metab 2007;8:554562.

    • Search Google Scholar
    • Export Citation
  • 2.

    Court MH, Hay-Kraus BL & Hill DW, et al. Propofol hydroxylation by dog liver microsomes: assay development and dog breed differences. Drug Metab Dispos 1999;27:12931299.

    • Search Google Scholar
    • Export Citation
  • 3.

    Hay Kraus BL, Greenblatt DJ & Venkatakrishnan K, et al. Evidence for propofol hydroxylation by cytochrome P4502B11 in canine liver microsomes: breed and gender differences. Xenobiotica 2000;30:575588.

    • Search Google Scholar
    • Export Citation
  • 4.

    Niimi Y, Inoue-Murayama M & Kato K, et al. Breed differences in allele frequency of the dopamine receptor D4 gene in dogs. J Hered 2001;92:433436.

    • Search Google Scholar
    • Export Citation
  • 5.

    Mealey KL, Bentjen SA & Gay JM, et al. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics 2001;11:727733.

    • Search Google Scholar
    • Export Citation
  • 6.

    Sartor LL, Bentjen SA & Trepanier L, et al. Loperamide toxicity in a collie with the MDR1 mutation associated with ivermectin sensitivity. J Vet Intern Med 2004;18:117118.

    • Search Google Scholar
    • Export Citation
  • 7.

    Revolution [package insert]. Groton, Conn: Pfizer, 2008.

  • 8.

    Tranquilli WJ, Paul AJ, Todd KS. Assessment of toxicosis induced by high-dose administration of milbemycin oxime in Collies. Am J Vet Res 1991;52:11701172.

    • Search Google Scholar
    • Export Citation
  • 9.

    Mealey KL, Northrup NC, Bentjen SA. Increased toxicity of P-glycoprotein-substrate chemotherapeutic agents in a dog with the MDR1 deletion mutation associated with ivermectin sensitivity. J Am Vet Med Assoc 2003;223:1434,14535.

    • Search Google Scholar
    • Export Citation
  • 10.

    Mealey KL, Munyard KA, Bentjen SA. Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of herding breed dogs living in Australia. Vet Parasitol 2005;131:193196.

    • Search Google Scholar
    • Export Citation
  • 11.

    Mealey KL, Bentjen SA, Waiting DK. Frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample population of Collies from the northwestern United States. Am J Vet Res 2002;63:479481.

    • Search Google Scholar
    • Export Citation
  • 12.

    Neff MW, Robertson KR & Wong AK, et al. Breed distribution and history of canine mdr1-1Δ, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage. Proc Natl Acad Sci U S A 2004;101:1172511730.

    • Search Google Scholar
    • Export Citation
  • 13.

    Hugnet C, Bentjen SA, Mealey KL. Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of collies from France. J Vet Pharmacol Ther 2004;27:227229.

    • Search Google Scholar
    • Export Citation
  • 14.

    Henik RA, Kellum HB & Bentjen SA, et al. Digoxin and mexiletine sensitivity in a Collie with the MDR1 mutation. J Vet Intern Med 2006;20:415417.

  • 15.

    Geyer J, Döring B & Godoy JR, et al. Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. J Vet Pharmacol Ther 2005;28:545551.

    • Search Google Scholar
    • Export Citation
  • 16.

    Mealey KL, Gay JM & Martin LG, et al. Comparison of the hypothalamic–pituitary–adrenal axis in MDR1–1Ä and MDR1 wildtype dogs. J Vet Emerg Crit Care 2007;17:6166.

    • Search Google Scholar
    • Export Citation

Advertisement

Breed distribution of the ABCB1-1Δ (multidrug sensitivity) polymorphism among dogs undergoing ABCB1 genotyping

Katrina L. Mealey DVM, PhD, DACVIM, DACVCP1 and Kathryn M. Meurs DVM, PhD, DACVIM2
View More View Less
  • 1 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610.
  • | 2 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610.

Abstract

Objective—To evaluate the breed distribution of the ABCB1-1Δ polymorphism in a large number of dogs in North America, including dogs of several herding breeds in which this polymorphism has been detected and other breeds in which this polymorphism has not yet been identified.

Design—Cross-sectional study.

Animals—5,368 dogs from which buccal swab samples were collected for purposes of ABCB1 genotyping.

Procedures—From May 1, 2004, to September 30, 2007, DNA specimens derived from buccal swab samples collected from 5,368 dogs underwent ABCB1 genotyping. These data were reviewed, and results for each dog were recorded in a spreadsheet, along with the dog's breed. The genotypes for each breed were tallied by use of a sorting function.

Results—The ABCB1-1Δ allele was identified in 9 breeds of dogs and in many mixed-breed dogs. Breeds that had the ABCB1-1Δ allele included Collie, Longhaired Whippet, Australian Shepherd (standard and miniature), Shetland Sheepdog, Old English Sheepdog, Border Collie, Silken Windhound, and German Shepherd Dog (a breed in which this mutation had not been detected previously).

Conclusions and Clinical Relevance—The ABCB1-1Δ polymorphism is associated with increased susceptibility to many adverse drug reactions and with suppression of the hypothalamic-pituitary-adrenal axis and is present in many herding breeds of dog. Veterinarians should be familiar with the breeds that have the ABCB1-1Δ polymorphism to make appropriate pharmacologic choices for these patients.

Abstract

Objective—To evaluate the breed distribution of the ABCB1-1Δ polymorphism in a large number of dogs in North America, including dogs of several herding breeds in which this polymorphism has been detected and other breeds in which this polymorphism has not yet been identified.

Design—Cross-sectional study.

Animals—5,368 dogs from which buccal swab samples were collected for purposes of ABCB1 genotyping.

Procedures—From May 1, 2004, to September 30, 2007, DNA specimens derived from buccal swab samples collected from 5,368 dogs underwent ABCB1 genotyping. These data were reviewed, and results for each dog were recorded in a spreadsheet, along with the dog's breed. The genotypes for each breed were tallied by use of a sorting function.

Results—The ABCB1-1Δ allele was identified in 9 breeds of dogs and in many mixed-breed dogs. Breeds that had the ABCB1-1Δ allele included Collie, Longhaired Whippet, Australian Shepherd (standard and miniature), Shetland Sheepdog, Old English Sheepdog, Border Collie, Silken Windhound, and German Shepherd Dog (a breed in which this mutation had not been detected previously).

Conclusions and Clinical Relevance—The ABCB1-1Δ polymorphism is associated with increased susceptibility to many adverse drug reactions and with suppression of the hypothalamic-pituitary-adrenal axis and is present in many herding breeds of dog. Veterinarians should be familiar with the breeds that have the ABCB1-1Δ polymorphism to make appropriate pharmacologic choices for these patients.

Contributor Notes

Dr. Mealey receives royalties from the application of the ABCB1 (MDR1) genotyping assay.

Address correspondence to Dr. Mealey.