Does ethnicity affect drug response?Veronika Litinski, MSc Medicinal Chemistry, MBA
Doctors have long been aware that family heritage and ancestry can majorly impact how people respond to medications. While not many people are aware of this, in the past, research studies were conducted on populations mostly of European descent. This created a significant gap in the representation of different races and ethnicities in studies, likely resulting in less effective treatment for those of diverse backgrounds. And it’s not just the medications. Dosage guidelines are based on the average, and people with different ancestries may require different doses. This issue is even more pronounced for mixed ethnic backgrounds.
What exactly does this mean?
Even properly prescribed medications can be ineffective or have adverse effects. Dosage guidelines based on averages are not a fit for every individual. Clinical guidelines that rely on race as a proxy for prescribing decisions can result in inaccurate assumptions. This is why it is integral that individual medical history and genetics should always be considered when determining medication and dosage.
Did you know? Geography and ancestry affect drug metabolism.
Just as genetics affect eye and hair colour, genetics also affect how a person responds to medications. There is no one-size-fits-all “average” even within a single ethnic population. Pharmacogenetic (PGx) profiles vary from person to person, which can significantly affect the effectiveness and safety of medications. The frequency of genetic variations influencing drug response dramatically varies across the world. For example, people of non-European ancestry have a higher prevalence of metabolism that does not match the historically assumed “average” levels.
People of Arab ancestry have:
- 8-10 times higher frequency of “ultrarapid metabolizers” for an enzyme called CYP2D6, which leads to faster elimination or activation of many medications, including antidepressants, some anti-nausea medications, and opioid painkillers.
- A high risk of treatment failure or potentially fatal side effects.
An analysis of Hawaiian, New Zealand and Australian indigenous populations revealed:
- An increased frequency of genetic variations leading to reduced metabolism of many critical medications.
- Up to 50% of Pacific islanders cannot convert clopidogrel (Plavix) to its active form, which prevents excessive blood clotting.
- Clopidogrel prevents heart attacks in most Europeans, but it is ineffective in preventing premature deaths in individuals with inherently reduced drug metabolism.
What does this mean if you’re a Canadian?
It’s important to consider your medical history and genetics. With a melting pot of immigrants and Indigenous tribes, there may be a higher percentage of individuals with reduced drug clearance. This is especially true for Indigenous communities due to ancestral migration patterns and geographic isolation. By considering each patient’s specific genetic makeup, only then can the most effective treatment be determined.
This all sounds great….but it’s important to note the following:
Making treatment decisions based on skin colour or attaching race labels is not only derogative and discriminatory but is an outdated practice. Accessible genetic testing technologies create a new standard of care called precision medicine, a more personalized, evidence-based way of prescribing.
The solution? DNA-guided prescribing for optimized results.
Many studies have shown that DNA-based drug selection and dosing help reduce the incidence of side effects and treatment failure. DNA-based prescribing guidelines developed by the globally recognized Clinical Pharmacogenetics Implementation Consortium aim to eliminate racial biases in prescribing. For example, doctors know that African Americans tend to metabolize the organ transplant drug tacrolimus much faster and often administer a higher dose. But in reality, based on individual genetics, only 70% of African Americans need a higher tacrolimus dose; the rest are likely to respond well to the standard amount. Many patients of Middle Eastern (14%) or Asian ancestry (44-55%) also require a higher dose when prescribed tacrolimus. Genetic guidelines can help everyone, regardless of their origin.
Even more benefits? DNA-guided prescribing reduces the rates of organ failure, avoids heart attacks and stroke, helps people to get to effective treatment of anxiety and depression faster, and improves pain and nausea management.
How can I get my DNA medication guide?
While many people are aware of DNA tests for ancestry analyses, these test results cannot be used for guiding medications. The testing technology used for ancestry analyses typically does not have the precision and sensitivity required for clinical pharmacogenetic applications. Pharmacogenetic tests target specific genes involved in drug metabolism, transport, and response and must analyze variations in each gene. Testing multiple ethnic variants allows for higher sensitivity, so the test results are valid for people of different backgrounds.
While many companies offer pharmacogenetic tests, you should find a provider that presents the best value for you. Your DNA does not change, so most likely, you will need only one pharmacogenetic test to use throughout life. However, genetic prescribing guidelines are constantly improving, so choose a vendor that offers high-sensitivity tests and provides report updates.