Pharmacogenetic Testing

Pharmacogenetics is the study of how differences (genetic variants) in a person’s DNA affect the way they respond to medication. Because genes are the blueprints for different functions in the human body, looking at these “blueprints” with testing can help healthcare professionals predict how a person may respond to a medication before it is taken. There are several methods for performing pharmacogenetic testing. 

On-site testing

Children’s Mercy is now performing pharmacogenetic testing in our clinical lab. Currently, two genes are reported and testing for other genes is being developed. Patients with cancer are the first group for which in-house testing is being performed. The Genomic Medicine Center and the Clinical Pharmacology Teams are collaborating to offer additional on-site pharmacogenetic testing to Children’s Mercy patients for other indications (transplant, gastroenterology, developmental & behavioral health), reducing the time it takes for testing and providing accessible reports.  

What testing is available?

Pharmacogenetic testing of the TPMT and NUDT15 genes is now available as part of in-house cancer next-generation sequencing (NGS) testing. These two genes are involved in breaking down thiopurine medications, commonly prescribed to kids with leukemia or inflammatory bowel diseases. Thiopurine medications include azathioprine, mercaptopurine, and thioguanine. This testing is performed to understand what dose of thiopurine medication the patient should be prescribed. Patients who have variants in these genes may need lower doses or alternative medications to avoid side effects.

How is the testing performed?

DNA is the genetic material in our cells that makes up the “recipes” (known as genes) which makes us who we are. Everyone’s genes are different and cause differences between people, such as whether certain drugs might be metabolized faster or slower. DNA from the patient’s cells is sequenced (“spell-checked”) and then compared to the DNA thousands of unrelated “control” individuals to look for differences in two genes, TPMT and NUDT15. Looking at genetic changes present in these genes may help provide important information about how the patient metabolizes specific drugs known as thiopurines.

What do pharmacogenetic results look like?

Pharmacogenetic testing uses a unique classification system, where each version of the gene is given a “star allele” name. Star(*) alleles can be defined by one or multiple genetic variants, and they may also share a variant or variants with other star alleles; however, each star allele is a unique combination of its own variants. The *1 allele is reported when no variants are detected, indicating the reference or “wildtype” allele with normal activity. Since one copy of each gene is inherited from each parent, we have two copies of each gene and two star alleles are included on the report.

In addition to the star alleles, the report will include an assessment of the enzyme or transporter protein function encoded by the gene. These functional groupings are used to make dosing recommendations or alternative medication recommendations. The recommendations in the report are based on peer-reviewed, evidence-based, freely available guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC). 

How can I find out more about pharmacogenetic testing?

For more information about clinical pharmacogenetic testing, or to learn how to order a test for a patient, please call (816) 915-5241.