A note for healthcare professionals.
A man in his early fifties with hypertension attends for review. He insists he has been taking his medication as prescribed, but his blood pressure remains well above target. He has spent several weeks on a medication that has done very little for him.
The scenario is familiar. There are clear protocols for changing an antihypertensive regimen once we know it is ineffective. There is far less guidance on how to avoid the situation in the first place.
Reactive versus proactive prescribing
Much of current practice was shaped in an era when there was no way to know how a patient would respond before the first dose. Guidelines are built on large clinical trials designed to identify what works for the greatest number of people — an entirely reasonable basis, but one that averages over patients whose genetic profile alters their response.
Pharmacogenomics offers a way to make some of those decisions in advance rather than after a failed trial of therapy.
Where the evidence currently supports testing
Genetic testing has been part of specialist practice for decades. What has changed is throughput — modern platforms screen large numbers of variants simultaneously rather than testing one suspected mutation at a time. Applications with the strongest evidence include:
- CYP2C19 and clopidogrel — loss-of-function variants reduce conversion to the active metabolite, attenuating antiplatelet effect. Increasingly tested following PCI, with prasugrel or ticagrelor as alternatives.
- HLA-B*5701 and abacavir — mandatory pre-prescription testing to avoid potentially fatal hypersensitivity.
- DPYD and fluoropyrimidines — now routine NHS practice before capecitabine or 5-FU to identify patients at risk of severe toxicity.
- TPMT/NUDT15 and thiopurines — established pre-treatment testing.
- CYP2C9/VKORC1 and warfarin — influence dose requirements, though DOACs have displaced warfarin for many indications.
- ADRB1 polymorphisms — associated with differential response to beta-blockade.
Where caution is warranted
The evidence base is uneven. It is robust for the drug–gene pairs above and considerably thinner for many others, including much of what is marketed direct to consumers. NHS England has signalled intent to expand pharmacogenomic testing, but adoption remains selective rather than universal — appropriately so, since testing must demonstrably improve outcomes to justify routine use.
Genotype is also one variable among several. Renal and hepatic function, age, comorbidity, drug–drug interactions and adherence frequently exert larger effects on response than any single polymorphism. In the hypertensive patient above, adherence, undiagnosed secondary causes, white-coat effect and salt intake all warrant consideration before genetics.
The practical position
Pharmacogenomics is neither a novelty nor a panacea. For a defined and growing set of drug–gene pairs, it allows prescribing decisions to be made proactively rather than reactively — reducing avoidable adverse effects and shortening the period before effective therapy is reached. For everything else, conventional clinical judgement remains primary.
The useful question for practice is not whether to adopt pharmacogenomics wholesale, but which specific tests have evidence strong enough to change what you do.
Further reading
The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes peer-reviewed, regularly updated dosing guidelines by drug–gene pair, and the NHS Genomic Medicine Service test directory sets out currently commissioned testing.
Testing with Rightangled
Rightangled's DNA tests examine markers relating to health risk and medication response, and our blood tests are processed by accredited UK laboratories. Results are reviewed by our clinical team, which includes GPhC-registered independent prescribers, with medical oversight from our doctor, Dr Abdullah.
Consumer genetic testing is a screening and awareness tool. Where a specific inherited condition is clinically suspected, NHS genetic services with genetic counselling remain the appropriate route, and patients should not alter prescribed medication on the basis of a consumer test result.
This article is intended as general information for healthcare professionals and does not constitute clinical guidance.
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