Pharmacogenomics is the study of drugs (pharmakon- the Greek word for poison or drug) and the genome. These two come together to explain why about 50% of medicines don’t work in some people and why they can sometimes be harmful, or even cause death. It’s our genetic makeup that’s often the cause.
The idea that the genetic makeup we inherit from our parents can affect how we respond to a foreign chemical goes back to Pythagoras, who described people becoming very sick by eating the broad bean Vicia Faba; “favism” is due to life-threatening red blood cell breakdown.
A more visible example of how our genetic makeup impacts our reaction to things we consume (and one you might be more familiar with) is the effect of alcohol on many people of Asian ethnicity. Alcohol is broken down in our body by enzymes to acetaldehyde, which is then further broken down by another enzyme to acetic acid.
The facial flushing, and runny eyes and nose are not due to a build-up of alcohol but a build-up of acetaldehyde. People exhibiting these symptoms lack the enzyme that breaks down acetaldehyde because of a single change in the gene that makes the enzyme which breaks down acetaldehyde.
Pharmacogenomics is the study of variations in our genome (DNA and RNA) that alter our response to drugs. It has nothing to do with disease susceptibility. It helps personalise medicine by studying DNA variations to better target a drug, or its dose, to improve health and not prevent toxic reactions.
It’s because of the Human Genome Project that we can now work out the genes that affect how a drug works or leads a drug to cause harm. Mapping the genome was the first step; we needed a picture of the genetic make-up of humans before pharmacogenomics could be possible.
DNA variations affect how well a drug is broken down by the liver, transported around the body to its site of action and the actual site the drug targets. The frequency of these drug genetic variations is very different between Caucasians, Asians, Africans and people from the Middle East. Virtually nothing is known about the genetic variations and their frequency in our Aboriginal population.
So why is pharmacogenomic testing not part of routine testing before a doctor writes a prescription? Well, for most drugs, a person’s genetic makeup plays a very small role in how a drug will affect her. Other factors such as her age or what stage she is in her illness are more significant.
But your genetic make-up is important for some drugs and Medicare funds tests for them. HIV medicine Abacavir, for instance, is not prescribed unless a genetic test is done to rule out a life-threatening reaction.
In some inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease), an old drug called azathioprine can cause a life-threatening drop in bone marrow cells in one in 300 people. A genetic test before starting treatment tells the doctor the best dose to avoid this toxic reaction.
More than meets the eye
There are many genes linked to drug toxicity or poor response. And whether or not we should test these genes before prescribing a drug is hotly debated.
All together, pharmacogenomic testing requires experts in genetic testing, pathologists, and experts in medicines (clinical pharmacologists and pharmacists). Just providing the results of a genetic test is not only inadequate but potentially useless. The results need to be interpreted and doctors need to be advised on what they should do to ensure patient safety. That’s the role of medicines experts.
Determining the cost-benefit of genetic testing for medicines needs large and international studies, the funding of which is difficult, especially in Australia.
Although the US FDA (Food and Drug Administration) has championed pharmacogenomics, and a 2008 Deloitte Economics report suggested such testing would deliver a net economic benefit of $12 billion over five years, the Australian government has not taken any action in this area.
But this is likely to change as our knowledge of drug-genome interaction increases and the cost of genetic testing falls. There will come a time when your doctor will not only test your liver or kidney function but also check your DNA variations to optimise the medicines you need to take and their doses.