ACE and the MDR1 Gene in Shelties

Did you know: ACE can be fatal to dogs with potential for the MDR1 gene mutation?  Breeds known to carry the mdr1 mutation include Australian Shepherds, Collies, English Shepherds, Longhaired Whippets, McNabs, Old English Sheepdogs, Shetland Sheepdogs, and Silken Windhounds.  Research has shown that three of every four Collies have at least one copy of the mutated gene.

Just to be safe, if you have a Sheltie and the Sheltie NEEDS SURGERY, THAT YOU ASK YOUR VET WHAT HE IS USING FOR PRE- OPERATIVE MEDICATIONS.  ACE is a VERY COMMONLY used pre-operative medication.

ACE can also cause prolonged and very deep sedation in dogs with the MDR1 mutation, so dosage reductions are recommended.

The MDR1 gene helps keep drugs which could cause toxic reactions in the brain, from getting into the brain. If a dog has one MDR1 gene and one normal gene (remember all genes come in pairs, so this gene pattern would be mutant-normal), that dog is more likely than a normal-normal dog to have a bad reaction. If a dog has two mutant MDR1 genes (mutant-mutant), the dog is likely, not just "more likely" to have a bad reaction. The problem exists with a limited number of drugs, including ACE. Perhaps most important, there is a big problem with ivermectin (Heartgard) in the mutant-mutant dogs. With mutant- normals, the problem is primarily with the large doses of ivermectin used to treat demodectic mange, rather than the normal preventive dose.

What happens is that one mutant gene lets a small amount of these drugs get into the brain where they cause toxic reactions. Two mutant genes let even more drug get into the brain and so can cause a really bad toxic reaction.

Here is a list of drugs which are known to have caused toxic reactions in MDR1 dogs. In addition to ivermectin and ACE, these are: butorphanol, used for pain; doxorubicin, vinblastine, vincristine and cyclosporin, used for chemotherapy; loperamide (Imodium), used for diarrhea; and digoxin, a heart medication. Other drugs may have caused problems in MDR1 dogs, but the evidence is still largely anecdotal and not established.

There is a test available to check for the presence of the MDR1 gene. It is a simple test, requiring only a cheek swab. The swab is collected at home, and mailed in for analysis. The results of your dog's test will be returned to you and should be provided to all your veterinary care-givers.

You can ask your vet for a test. If he doesn't have a test kit, ask him to request an MDR1 test kit (with instructions) from:

Washington State University
College of Veterinary Medicine
Clinical Pharmacology Laboratory
P.O. Box 609
Pullman, WA 99163-0609
Phone/FAX-509.335.3745
or visit WSU on the web at: http://www.vetmed.wsu.edu/depts-VCPL/test.asp

You can order one yourself, but I think they are packaged in sets of 4 for $60.

The veterinary school at the University of Washington also has more in-depth info on the MDR1 mutataion, which you can find if you go to http://www.vetmed.wsu.edu/depts-VCPL/.

How frequent is the MDR1 mutation in the breeds mentioned above? A 2004 article (highly technical) noted that in Collies, the likelihood of a mutant-mutant pattern is almost 25%, and the chance of having one mutant gene is almost 50%. In Australian Shepherds, the chance of one mutaant gene is about 30%, with the chance of a double mutant pattern, just under 2%. The risk is slightly greater for mini's. For anyone who would like to read this article in its entirety, you can go to: www.pnas.org/cgi/doi/10.1073/pnas.0402374101.

Thanks to Kim K for the great reminder!