What is pharmacogenomics?

In this explainer episode, Dr Jude Hayward, GP and Principal Clinician for Primary Care at Genomics England, explains what we mean by pharmacogenomics.

You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.

If you’ve got any questions, or have any other topics you’d like us to explain, let us know on [email protected].

You can download the transcript or read it below.

Florence: [00:00:00] What do we mean by pharmacogenomics? My name is Florence Cornish, and today I'm here with Jude Hayward, who is principal clinician for primary care here at Genomics England, and she is going to be telling us much more about the topic.

So, Jude, thanks so much for being here. It's great to have you.

Jude: Thank you, Florence, and thank you for the invitation, delighted to be here. I'm Dr. Jude Hayward. I am principal clinician for primary care, and that's my role within Genomics England. I am a GP, and I work half-time as a GP, and I also work as a GPER, a GP with an extended role in clinical genetics. I have other roles nationally, working as primary care lead for the Genomics Education Programme, and also representing genomic medicine for the Royal College of General Practitioners.

And really, this is through my interest in implementing genomic medicine into primary care, supporting my primary care colleagues, and this most recently has led me to have an interest in pharmacogenomics.

Florence: [00:01:00] And so, Jude, when we say the word pharmacogenomics, we're actually saying a combination of two words, right? We're saying pharmacology, combined with genomics.

And so, it might be helpful if we could start by explaining each of those on their own first. Could you talk through what we mean by the word genomics?

Jude: Yes, absolutely. And genomics will be familiar to the listeners of the podcast. The genome is our full set of DNA. Part of the genome is genes, and each of these genes acts as an instruction, so the genome acts as an instruction manual for everything about us. Genomics is the study of this genome, and genomic medicine is how the genome can impact their health.

Florence: Mm-hmm.

Jude: Moving on to pharmacology, this is the study of how medicines and chemicals interact with and affect the body and how we process and handle medications within our bodies.

Florence: And so if we combine both of these together, genomics and pharmacology, we get this pharmacogenomics, which is presumably kind of a mashup of the two, right? Looking at how a person's genes can affect their response to medicines.

[00:02:00] Would you say that that's accurate? Can you tell us a little bit more about it?

Jude: Yes. I think that's a great description, Florence. So yes, essentially, pharmacogenomics is a study of how a person's genome interacts with the way that they respond to medication. So, it is a type of personalized medication. We all carry the same genes. We all carry the genes which affect the way that we respond to medications, and we carry changes or variants in these genes which affect the way that we handle certain medications.

[00:02:30] But these only become relevant if we are prescribed a medication which is going to interact and form what's called a gene-drug pair.

Florence: Yeah. So, tell me a little bit more about that. Why do medicines work differently for different people? Why do we see this happening?

Jude: Well, there's a variety of different reasons for this. There's multiple factors which affect how an individual may respond or react to a certain medication. So pharmacogenomics is one, and even there, there are multiple different variants that may occur. And so there are multiple different ways in which our genomic information, our genomes, can affect how we respond.

[00:03:00] But in addition to that, there's all sorts of other things as well. So, what we eat affects how we might react to medication. Other genes, maybe other conditions that we have will affect how we react to a medication, other medications we're taking will affect how we react to a medication and there's all sorts of other environmental factors as well.

Florence: Do you have any real-world examples that we know of, of genes that people have that might affect their response to specific medications?

Jude: [00:03:30] Yes. The one that I'm going to talk about is one called CYP2C19. Now, that's how it's said, but it's actually spelt C-Y-P-2-C-1-9, which is just essentially a reference number for the gene CYP2C19.

This is one that people may have heard of because it's been in the news over the last couple of years. So, we know that if people have a stroke or a mini stroke, that at the moment the usual practice is to offer them a prescription of a medication that can thin their blood down, and one of the common ones is one called clopidogrel.

Florence: [00:04:00] Mm-hmm.

Jude: And this has been prescribed for people for many, many years, and it can help reduce the chances of them having a second stroke or a second TIA. However, certain variants in the CYP2C19 gene can affect the way that people process clopidogrel in the body. And there are some groups of people, and I can go on to discuss this in more detail, but there are some groups of people in whom it is less effective.

[00:04:30] And therefore, if we test the CYP2C19 gene, it can give us information as to whether somebody should be given a standard dose of clopidogrel or whether it's less likely to be effective for them, in which case they may be recommended an alternative medication or even a different dose of clopidogrel.

Florence: You mentioned earlier something called a gene-drug pair. That's a term I've actually never heard before. Could you tell me a little bit more about what that is?

Jude: So a gene-drug pair is formed when somebody has a variant in a relevant gene and they are prescribed a medication, and the medication prescribed is affected by the variant that they have in that gene.

Florence: [00:05:00] Right.

Jude: So in that instance, a gene-drug pair is formed. There's two main ways that it may be important. It may be that it means that somebody is more or less likely to develop a side effect to that medication, or it may give us information that the medication is going to be more or less effective in them.

Florence: Right.

Jude: It can never tell us in a black-and-white way that somebody will or won't have a reaction or if they will or won't benefit from the medication, but it helps us predict who's more likely to have a side effect and who is more likely to benefit.

Florence: And so, tell me about how a specific genetic variant can mean that a drug is less or more effective in that individual.

Jude: So, I'm going to carry on with the example of CYP2C19 that we've been talking about. The CYP2C19 gene codes a protein, which is an enzyme, which processes certain medications in the body.

[00:06:00] So variants affect the level of function of this enzyme. So certain variants mean that the enzyme works much more quickly and therefore processes or metabolizes medications much more quickly.

And if that happens, people are termed rapid metabolizers or ultra-rapid metabolizers because of the speed that they're metabolizing. Conversely, other variants in the CYP2C19 gene can reduce the function of that enzyme, which then means that people metabolize or process medications more slowly and then tend to be called poor metabolizers.

So people who are poor metabolizers of clopidogrel, they don't process clopidogrel to the active medication in the body, and so there is less available of the active medication in the body and therefore that means that it's less effective for them.

Florence: Right. And all of that information will affect the amount that they're prescribed or the drug that they're prescribed?

Jude: [00:07:00] It could affect either. So clopidogrel, the guidance that exists at the moment tends to recommend an alternative medication. But in some circumstances, if an alternative medication isn't appropriate or isn't safe either, then it may be a change in dose that's recommended. But this could vary between medication and vary between gene.

Florence: So is pharmacogenomics being used in the clinic day to day to help inform our routine care?

Jude: Yes. There are a few examples where pharmacogenomic testing is recommended and done in the clinic.

[00:07:30] One is a gene called DPYD, and variants in this gene can help predict whether someone has a serious, possibly even fatal reaction to certain chemotherapy agents.

Another example is a gene called MT-RNR1, which helps predict whether someone may develop hearing loss to certain very strong broad-spectrum antibiotics. So yes, there are already examples where a test is available to be ordered, and it can help guide choice of medication and predict serious significant side effects.

Florence: [00:08:00] Well, I think we'll finish there. Thank you so much, Jude, for coming on. It's been so interesting.

Jude: Thank you very much, Florence. I've really enjoyed it. And thank you very much for the invitation and for having me on the podcast.

Florence: If you want to hear more explainer episodes like this, you can find them on our website at www.genomicsengland.co.uk or wherever you get your podcasts.

We'd also love to hear what you think. Do you have experience with any of the topics we've covered, or is there anything else you want us to explore?

[00:08:30] Let us know by commenting wherever you listen. See you next time