Multiple Drug Sensitivity (MDR1)
Multiple Drug Sensitivity (MDR1) is characterized by adverse reactions to certain classes of drugs including the parasiticide Ivermectin, and gastroprotectant and anti-cancer medications including Loperamide (Imodium) and Doxorubicin. Other drugs that can cause adverse reactions on dogs with MDR1 are Acepromazine, Butorphanol, Cyclosporine, and Spinosad (Comfortis). Adverse reactions can include vomiting and diarrhea, lethargy, tremors, ataxia, excess salivation, seizures, respiratory arrest, and coma. Diagnosis is often made only after a dog has had an adverse reaction to a problem drug. However, genetic testing will identify whether your dog is at risk so that you can avoid administering potentially problematic drugs. MDR1 results from a mutation in the ABCB1 gene. Dogs in which one or both copies of the gene have this mutation are at risk of exhibiting adverse drug reactions. This mutation is particularly common in herding breeds but is also seen frequently in many other breeds and in mixed breed dogs.
Breeds affected: May occur in almost any breed and in mixed breed dogs, but most common in herding breeds including Australian Shepherds, Collies, Border Collies, English Shepherd, Shetland Sheepdog, Smooth Collie, and German Shepherd Dogs.
References:
Mealey KL, Bentjen SA, Gay JM, Cantor GH. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics 11(8):727-33., 2001.
Gramer I, Leidolf R, Döring B, Klintzsch S, Krämer EM, Yalcin E, Petzinger E, Geyer J. Breed distribution of the nt230(del4) MDR1 mutation in dogs. Vet J. 189(1):67-71, 2011.
Gene: ABCB1
Explanation of DNA Test Results
Phenotype: Affected dogs exhibit adverse reactions following administration of certain drugs, such as ivermectin, acepromazine, loperamide, cyclosporine, and others. Signs may include vomiting and diarrhea, lethargy, tremors, ataxia, excess salivation, seizures, respiratory arrest, and coma.
Dogs with N/N genotype are not expected to have multidrug sensitivity. They cannot transmit the risk variant to their offspring.
Dogs with N/MDR1 genotype may exhibit multidrug sensitivity and will transmit the risk variant to 50% of their offspring. Matings between two heterozygous dogs will, on average, produce 25% of puppies with multidrug sensitivity.
Dogs with MDR1/MDR1 genotypes are homozygous for the risk variant and will exhibit multidrug sensitivity even at low doses. Any of there offspring will have at least one copy of the risk variant and will be at risk of exhibiting multidrug sensitivity.
Samples are then sent to the University of Missouri College of Veterinary Medicine where the samples will be processed by the Small Animal Molecular Genetics Lab. Results will be forwarded to the OFA, and the OFA will issue the resulting report to the owner.
The fee for each test includes the test kit, laboratory processing, and subsequent registration in the OFA databases.