Page 14 - Chow LIfe - Fall 2021.pdf

By Sharon M Albright, DVM, CCRT
March 2020

The AKC Canine Health Foundation (CHF) is a CHF Grant 02242: Understanding the Genetics of
non-profit organization dedicated to advancing the Adverse Drug Reactions in Sighthounds
health of all dogs and their owners through funding
scientific research and dissemination of health CHF Grant 02529: Understanding the Genetics of
information. As the world’s largest funder of research Adverse Drug Reactions in Sighthounds: Phase II
exclusively for dogs, CHF works with veterinarians, CHF Grant 02803-MOU: Genetics of Adverse
researchers, and parent clubs like the Chow Chow Reactions to Anesthetic and Sedative Drugs in
Club, Inc. to find and fund projects with the greatest Chow-Chows
potential to impact canine health. With help from
CHF funding, exciting progress has recently been
made in understanding the genetics of adverse Before we dive into these studies, let’s review some
drug reactions and variations in how individual genetics and physiology basics –
dogs respond to anesthetic and sedative drugs. When an organism such as a dog or human
This research can move toward more personalized expresses a gene, it is simply manufacturing the
veterinary medicine, using objective data to gene’s corresponding protein. There are two major
determine the safest and most effective treatments steps in this process:
for any individual dog.
During transcription the gene’s DNA information
Individual variation in drug response - is transferred to a messenger RNA (mRNA)
For years, veterinarians and dog owners have molecule.
known that certain dog breeds respond differently During translation that mRNA molecule is
to commonly used medications. The observation of translated into a sequence of amino acids creating
abnormal responses by Collies and related breeds to a protein.
some chemotherapy drugs and common antiparasitic
drugs like ivermectin led to the discovery of the Cytochrome P450 (CYP) enzymes are a family
multiple drug resistance 1 (MDR1) gene mutation of proteins that are responsible for creating
in 2001. Researchers at Washington State University and breaking down (metabolizing) numerous
identified a mutation in the MDR1 gene that resulted substances in the body. Variations in the genes
in decreased levels of an important protein that helps making these enzymes affect the amount and
pump chemicals, like medications, out of the brain function of the enzymes produced. If a cytochrome
and back into the blood stream. With fewer protein P450 enzyme is present in low quantities or
pumps available to control drug levels in the central metabolizes a drug slowly, the drug stays active
nervous system, drug concentrations reached higher longer and less is needed to get the desired effect.
levels and lasted longer, resulting in exaggerated and Conversely, if there are high levels of a cytochrome
negative responses to these medications. Thankfully P450 enzyme or a drug is quickly metabolized,
a simple cheek swab test for this mutation became then a higher dose might be needed to be effective.
available in 2004 and it is now common practice
in veterinary medicine to test dogs for the MDR1
mutation prior to prescribing certain medications. Understanding adverse drug reactions in
Sighthounds -
It has also been noted that Greyhounds, other
sighthounds, and some Chow Chows take longer CHF-funded researchers at the University of
to recover from certain sedative and anesthetic Washington set out to identify the genetic mutations
drugs compared to other breeds. Since the MDR1 and mechanisms responsible for slower anesthetic
mutation does not explain these dogs’ abnormal and sedative recovery in Sighthound breeds. They
responses, CHF and its donors have invested more measured the amounts of eleven cytochrome P450
than $300,000 in research to investigate additional enzymes in four dog breeds and mixed breeds and
mechanisms and genetics that could explain such found breed-specific variations in the quantity of one
responses. specific enzyme denoted CYP2B11. This enzyme was
most abundant in hounds and Beagles, present in
For more information, visit akcchf.org/ intermediate levels in mixed breeds and Chihuahuas,
generalRPA to view these studies and their and present in the lowest levels in Greyhounds.
resulting peer-reviewed publications: CYP2B11 was now a cytochrome P450 enzyme
12