Aster Witvliet, BSc Liberal Arts and Sciences, Science major
Have you ever taken a medication that had a nasty side effect? Or have you taken a medication that appeared to do absolutely nothing to alleviate your health complaint? Not all people respond the same to taking a specific drug; for some people, it might work well, while it might not work at all for others or come with troubling side effects. Your genes might be to blame for the side effects and reduced effectiveness of your medication, as your genes can influence your body’s response to a drug . The field of pharmacogenetics studies this relationship between people’s genes and their response to medications . Research in this field can help personalise treatment, as looking at someone’s genetics can help a physician choose a medication that is likely to be effective and avoid medication that is likely to be ineffective or cause major side effects .
One case where looking at the relationship between genetics and medication has already proven beneficial is treatment with the immunosuppressant drug azathioprine. Azathioprine reduces the immune system’s activity, which can be useful in treating patients with an autoimmune disorder where the immune system has started attacking the body [2, 3]. The enzyme thiopurine methyltransferase (TPMT) is involved in the metabolism of azathioprine . Some people have a mutation in their TPMT genes, which causes their TPMT enzymes to work less well, or sometimes even not work at all . Patients with lower or no TPMT enzyme activity have a severely increased risk of bone marrow suppression, a life-threatening side effect of azathioprine . A patient that is found to have deficient TPMT enzymes upon genetic testing can then be prescribed a lower dose of azathioprine or receive an alternative medication to prevent life-threatening side effects [2, 3].
The case of azathioprine and the TPMT enzyme shows the potential power of personalising treatment based on a patients’ genetics. Currently, pharmacogenetics is starting to become a part of clinical practice. In the Netherlands, a general practitioner or specialist can have patients genetically tested for the generation of a so-called DNA-passport by the Erasmus MC . For this DNA-passport, the activities of over 20 enzymes are investigated, and the results can have implications for dozens of medications. However, concerns about the evidence base and healthcare workers’ lack of knowledge on pharmacogenetics remain important roadblocks to wide implementation . In the future, as evidence base for pharmacogenetics strengthens and physicians become more familiar with its potential, you might be saved from serious side effects if your doctor takes a quick glance at your genetics.
 Drew, L. Pharmacogenetics: The right drug for you. Nature 537, S60–S62 (2016).
 Wang, L. & Weinshilboum, R. Thiopurine S-methyltransferase pharmacogenetics: insights, challenges and future directions. Oncogene 25, 1629-38 (2006).
 Dewit, O., et al. Limitations of extensive TPMT genotyping in the management of azathioprine-induced myelosuppression in IBD patients. Clinical biochemistry 44, 1062-1066 (2011).
 Erasmus MC. Farmacogenetica [Internet], cited 2021 03-31. Available from: https://www.erasmusmc.nl/nl-nl/patientenzorg/laboratoriumspecialismen/farmacogenetica
 Slob, E., et al. What do we need to transfer pharmacogenetics findings into the clinic? Pharmacogenomics 7, 589-592 (2018).