Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup. (U.S. National Library of Medicine)
It’s early days for pharmacogenomics, the study of how genes affect a person’s response to drugs. Our understanding of how particular genes and sets of genes interact with medications is still rather crude, but advancing at a rapid pace. Interestingly, much of this information is openly and immediately available through the internet, the primary mechanism for the democratisation of medical knowledge.
Before I continue with some specific examples, I do need to give a couple of caveats:
- Not everything you read on the internet is true and/or accurate. In fact, my research shows that “the seeds of misinformation” + “the existence of confirmation bias” + “a large enough community” = “confident ignorance”. Sorry to break that to you. 🙂
- It’s such early days for this emerging science that I would urge very great caution in making treatment decisions based on our current knowledge base. I’m much more interested in exploring what pharmacogenomics will become in the next few years than what it is today.
With that said, it remains fascinating how much pharmacogenomics information an engaged patient has access to today. For around US $100-$200, you can purchase a SNP sequence of your autosomal DNA (i.e. a basic DNA test). Having done that, services such as 23andme can produce a “Drug Response” report for your genome. See an example below:
This report shows that the patient has an increased sensitivity to warfarin (a blood thinner used to prevent blood clots from forming or growing larger in your blood and blood vessels), due to variations of the CYP2C9 and VKORC1 genes. These variations can decrease a person’s ability to break down warfarin, which causes the drug’s effect to last longer, resulting in the need for lower doses.
If you want to get more advanced as an engaged patient, I’ve found the LiveWello service to be incredibly useful and absolutely fascinating. Take a look at the following report:
This is showing the drug response report for Zofran (a drug used to prevent nausea). It shows that Zofran is more likely (although not 100% certain) to produce an increased response (relative to the average) in the patient with this genome.
By drilling down on the CYP2D6 gene link shown in the report above, the following highly interesting information is available:
The CYP2D6 gene encodes members of the cytochrome P450 superfamily of enzymes. These enzymes catalyze many reactions involved in drug metabolism. About 25% of drugs are metabolized by this gene.
Genes that encode for specific liver enzymes involved in drug metabolism, can be activated, deactivated, or influenced by various drugs. Drug companies use genetic tests to predict how a particular person will respond to various prescription and non-prescription drugs. Based on their genotypes people fall into four categories:
Poor metabolizers are people who break down drugs at a slower rate than others because they have little or no enzyme function. Poor metabolizers may experience adverse drug reactions while taking their medications at the typically recommended doses.
Intermediate metabolizers break down drugs at a rate somewhere between the poor and extensive metabolizers.
Extensive metabolizers have typical enzyme function and metabolize drugs at the expected rate. Most people are extensive metabolizers.
Ultrarapid metabolizers break down drugs at a greater than normal rate. People with this geneotype might require greater than the recommended dose of a medication to achieve the desired therapeautic effect.
Reading these reports it becomes obvious that the way we have traditionally prescribed medications is pretty crude. During the latter stages of clinical trials we give a potential drug to a cohort of patients, usually with little or no understanding of their genome, and observe the outcomes. The success of the drug becomes a statistical trade-off between the extent to which drugs showed efficacy, versus the reported side-effects. If, statistically speaking, a drug is effective but has a manageable level of side-effects and doesn’t cause death, then we can start to safely make use of it.
However, pharmacogenomics, one of the foundations of precision / personalised medicine, potentially gives us a new approach. Rather than looking statistically at the drug response across large patient cohorts, we can begin to look at the individual responses of patients. Some patients will need larger does of a particular medication, some smaller doses. Other patients should potentially avoid particular medications altogether. Perhaps in the future we won’t always need to wait until they have an allergic reaction to know that.
So, with the availability of such information to engaged patients, how should we begin to incorporate the use of pharmacogenomic knowledge into the everyday prescribing of medications? Unfortunately, this turns out to be a very complex question…
Whilst the use of pharmacogenomics has taken off in (and arguably been driven by) oncology, it turns out to be a topic that most GPs / Primary Care Physicians and even Specialists have barely heard of, let alone are ready to adopt into current practice. I do understand that it’s very early days for this emerging science, but some of my attempts to discuss pharmacogenomics with GPs have been met with a dismissive and even disdainful attitude. Yeah, I know I’m not normal!
The majority of health providers are not deeply trained in genetics, and some are threatened by recent advancements in medical knowledge that are complex to understand. Engaged patients raising these issues can therefore (in my experience) be met with highly paternalistic responses, reminding the patient of their place and reasons why the knowledge in question couldn’t possibly be correct and/or applicable.
The problem, however, is this. When patients are told by doctors that their knowledge isn’t important or valid then they gather together. We’re seeing this time and again with some of the internet’s better Digital Health Communities. It’s what I call “the rise of the expert patient“. Sick of being told that they don’t know what they are talking about and couldn’t possibly understand, engaged patients gather together to discuss, learn and synthesise the latest knowledge. In many cases this includes the very latest medical research papers. LiveWello is a great example of this.