Pharmacogenetics helps explain why patients respond differently to the same treatment and supports more personalised prescribing

In clinical practice, it is not uncommon to encounter patients who either do not respond to medications as expected or experience unwanted side effects. Pharmacogenetics — the study of how genes influence drug metabolism — offers valuable insights into these differences and can help guide more personalised treatment decisions.

For example, commonly prescribed medications such as statins, antidepressants and pain relievers depend on enzymes from the Cytochrome P450 family, as well as specific drug transporters, to be processed by the body. Genetic variants affecting proteins such as CYP2D6, CYP2C19 and SLCO1B1 can alter drug metabolism, leading either to increased side effects or reduced efficacy.

In fact, around 10–25% of individuals carry genetic variants that significantly affect the function of these enzymes, influencing how they respond to certain medications.

A practical example: statins

Statins, which are used to lower cholesterol, are generally well tolerated. However, approximately 21% of individuals carry a genetic variant in the SLCO1B1 gene. This gene encodes the OATP1B1 protein, which helps transport statins into liver cells.

Variants such as SLCO1B1*5, also known as p.Val174Ala, can result in higher levels of statins circulating in the body, increasing the risk of muscle pain, known as myalgia, or, in rarer cases, muscle damage, known as myopathy.

A pharmacogenetic test can identify individuals carrying this variant, allowing clinicians to select an alternative statin or adjust the dosage to reduce the risk of side effects.

Escitalopram and antidepressants

Another example is a patient who has been prescribed escitalopram for depression but does not show any improvement, despite following the treatment plan correctly.

Escitalopram is metabolised primarily by the CYP2C19 and CYP2D6 enzymes.

If the patient carries a genetic variant that makes them an ultra-rapid metaboliser, the drug may be broken down too quickly to be effective. A pharmacogenetic test can reveal this profile, helping the clinician choose an alternative antidepressant that does not rely on the same metabolic pathways.

Pharmacogenetics of codeine

Codeine is another medication influenced by CYP2D6 activity. It is commonly prescribed as a pain reliever or cough suppressant, but its effectiveness depends on being converted into morphine in the body — a process regulated by CYP2D6.

Patients who are slow metabolisers may find codeine ineffective, while ultra-rapid metabolisers may experience a short but exaggerated effect, with a higher risk of toxicity.

Knowing a patient’s CYP2D6 status can help avoid these issues and support more effective treatment choices.

Better outcomes for patients

By incorporating pharmacogenetic testing into clinical practice, healthcare professionals can personalise drug selection and dosing according to each patient’s unique genetic profile.

This approach can help reduce the likelihood of adverse effects and improve treatment efficacy.

Currently, only a limited number of laboratories in Switzerland offer these tests, making pharmacogenetics a valuable resource for personalised patient care.

Author: Dr Pierre-Alain Menoud
Title: FAMH in Medical Genetics at Unilabs Switzerland