What is pharmacogenomics?
Have you ever been prescribed a drug that works wonders for other people, but did nothing for you or caused major side effects? The explanation could lie in your genes. Pharmacogenomics is the science studying how each person’s genetic variants influence the way their body absorbs, metabolises and responds to drugs.
We don’t all metabolise drugs at the same rate. While a standard antidepressant dose may be perfect for one person, for another it may be insufficient or even toxic. Pharmacogenomics moves prescribing from “trial and error” to precision medicine.
The key genes: the CYP family
Most drugs are metabolised in the liver through a group of enzymes called cytochrome P450. The most relevant in pharmacogenomics are:
CYP2D6
It metabolises about 25% of all prescribed drugs, including codeine, tramadol, tamoxifen and many antidepressants (fluoxetine, paroxetine, venlafaxine). Depending on your genetic variants you may be:
- Ultrarapid metaboliser — you convert the drug too fast; codeine, for example, turns into morphine at dangerous doses.
- Normal (extensive) metaboliser — the standard dose works as expected.
- Intermediate metaboliser — may need dose adjustment.
- Poor metaboliser — the drug accumulates, increasing toxicity risk.
CYP2C19
It is crucial for the metabolism of clopidogrel (antiplatelet drug used after coronary stents). A CYP2C19 poor metaboliser does not correctly activate clopidogrel, which can increase thrombosis risk. CPIC clinical guidelines already recommend genotyping CYP2C19 before prescribing this drug.
It also affects proton-pump inhibitors (omeprazole) and antidepressants such as escitalopram and sertraline.
CYP2C9 and VKORC1: the warfarin case
Warfarin is one of the world’s most used anticoagulants, but it has a very narrow therapeutic margin: too little and it doesn’t prevent clots; too much and it causes bleeding. Variants in CYP2C9 (which metabolises it) and VKORC1 (its molecular target) explain up to 40% of the variability in required dose between patients. The FDA includes pharmacogenomic information in warfarin’s drug label.
Beyond CYPs: other relevant genes
- DPYD — variants reducing this enzyme’s activity cause severe toxicity with 5-fluorouracil, a common chemotherapy drug. Prior genotyping is already mandatory in the European Union.
- HLA-B*57:01 — predicts severe hypersensitivity to abacavir (HIV antiretroviral).
- SLCO1B1 — variants associated with statin-induced myopathy.
- TPMT/NUDT15 — essential for adjusting azathioprine and mercaptopurine doses in autoimmune diseases and leukaemias.
Is pharmacogenomics for me?
The short answer is yes. We all take medicines at some point in our lives. Knowing your pharmacogenomic profile once will stay with you forever: every time a doctor needs to prescribe something, they can check your data and choose the optimal drug and dose for you.
It is especially useful if:
- You take several drugs simultaneously (polypharmacy).
- You have experienced unexpected side effects.
- You need anticoagulants, antidepressants, chemotherapy or pain treatment.
- You want to prevent adverse reactions before they happen.
Your pharmacogenomic profile at OmicaLabs
Our personal genome (GenePortal) report includes a complete pharmacogenomic panel with the main genes recommended by CPIC and PharmGKB, interpreted by clinical genomics specialists. A single analysis, information for life.
Discover how your genes can improve your relationship with medicines. Request your report here.