Study Highlights How Common Genetic Variants Are that Impact Drug Processing

The majority of us have at least one genetic variant in the CYP2C19 gene that may alter how our bodies process certain commonly used medications, according to a new study from 23andMe and the University of California, San Francisco (UCSF) School of Pharmacy. Most people, however, don’t know about these variants because this kind of genetic testing, called pharmacogenetic (“farm-uh-ko-genetic”) testing, isn’t yet widely used. 

The 23andMe study, published in the online journal Clinical and Translational Science, confirms previous smaller studies and underscores the potential benefit that widespread preemptive pharmacogenetic testing could have.

“Our study reaffirms how common these variants are that affect how we metabolize certain medicines, and how many people could potentially benefit from knowing about them,” said Alison Chubb. “This is information they could share with their doctor if they ever need one of the relevant medications.”

Alison is a Senior Product Scientist at 23andMe and senior author of the study. 

The study comes in the wake of an FDA 510(k) clearance that modifies the agency’s previous clearance of 23andMe’s CYP2C19 Drug Metabolism report by removing the need for confirmatory testing and allowing the company to provide interpretive drug information based on genetic factors for two medicines, clopidogrel, and citalopram.

This graphic shows how common the CYP2C19 varaints are among 23andMe customers of different ethnicities.
CYP2C19 and Drug Metabolism

When it comes to medicines, we know that one size doesn’t necessarily fit all. Different people may respond differently to the same medicine due to factors like their age, weight, liver and kidney function, diet, or even other medicines they might be taking. But for some medicines, genetic factors also play a role, and the CYP2C19 (often pronounced “sip-two-see-19”) gene is one example.

The CYP2C19 gene provides the instructions for making the CYP2C19 enzyme, which is primarily found in the liver and helps the body process (or “metabolize”) important medications. For example, clopidogrel is a blood thinner for treating and preventing heart attacks, while citalopram is an antidepressant. The enzyme also helps process over-the-counter treatments for acid reflux and ulcers called proton pump inhibitors. This graphic offers examples of the type of medication that are affected by the CYP2C19 Enzyme.

Specific inherited variants in the CYP2C19 gene impact how well the CYP2C19 enzyme works. People who have these variants may process certain medicines faster or slower than normal, which in turn may affect how well the medicines work or the chances they’ll cause side effects. For a few medicines, the potential impact of CYP2C19 variants is so strong that the FDA-authorized drug labels include a warning or dosing recommendation based on CYP2C19 genotype. To help summarize these actionable gene-drug effects, the FDA has recently published a useful table of pharmacogenetic associations for healthcare providers that includes CYP2C19 and other genes. 

23andMe Study Details

Researchers wanted to know just how common CYP2C19 variants are among 23andMe participants who have consented to research, and how someone’s ancestry affects their chance of having one. The study looked at the distribution of the three most common CYP2C19 variants across nine self-reported ancestry groups and found that overall, almost 60% of the 2.29 million participants had at least one variant that could affect how they process certain medicines.

Two of the variants studied result in a CYP2C19 enzyme with decreased activity, and people with these variants may process some medicines slower than normal. These variants were most common in participants with East Asian, South Asian, and Hawaiian or other Pacific Islander ancestry. 

In contrast, the third variant that researchers looked at results in a CYP2C19 enzyme with more activity than normal, so some people with this variant may process certain medicines faster than normal. This variant was most common in people of European, African American, Ashkenazi Jewish, and Middle Eastern descent.

Although people of Hispanic or Latino descent had the lowest rate of CYP2C19 variants compared to other groups, they still had a 50% chance of having at least one variant. The take-home message is that these pharmacogenetic variants are common across all ancestries, which is quite different from the distribution of many disease-related genetic variants that are often rare and ancestry-specific.

But what is the potential real-world impact of these findings? To answer that we need to know how many people actually use the medicines that depend on CYP2C19 metabolism. To get some insight into this question, the researchers looked at prescription rates in the UCSF health system (2012-2019) and found that about 16% of patients had been prescribed one or more medications metabolized by CYP2C19. They then extrapolated from the 23andMe variant frequencies and calculated that more than 120,000 prescriptions in the UCSF system were likely written for people who had non-normal CYP2C19 metabolism and might have benefited from knowing about their CYP2C19 variants before they started their medicines, so they could discuss with their doctors available options based on their genetic result.

Pharmacogenetics Reports at 23andMe

In October 2018, the FDA granted 23andMe authorization to report CYP2C19 variants and predicted metabolizer status directly to consumers, along with additional variants in seven other genes that also impact drug metabolism. The initial 23andMe Pharmacogenetics* reports, including the CYP2C19 Drug Metabolism report, will be available later this year. 

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*The 23andMe PGS test uses qualitative genotyping to detect 6 variants in 3 genes in the genomic DNA of adults from saliva for the purpose of reporting and interpreting information about the processing of certain therapeutics to inform discussions with a healthcare professional. It does not describe if a person will or will not respond to a particular therapeutic and does not describe the association between detected variants and any specific therapeutic. Results should be confirmed in a clinical setting with independent genetic testing before taking any medical action.  Warning: Test information should not be used to start, stop, or change any course of treatment and does not test for all possible variants that may affect metabolism or protein function. The PGS test is not a substitute for visits to a healthcare professional. Making changes to your current regimen can lead to harmful side effects or reduced intended benefits of your medication, therefore consult with your healthcare professional before taking any medical action. For a complete list of the 6 variants tested, visit Pharmacogenetics Important Test Information.