Denmark Research Finds that a Combination of Genes Causes Medication Side Effects and Deficiencies in Most Patients

Medications’ side effects and inadequacies are caused by the effects of multiple genes in most patients, new research shows

Precision medicine is an emerging field of study that provides treatment to individual patients based on their unique genetic traits and physiology. This is different from how medicine is widely practiced, with medications and treatments given that have been tested on a large group of individuals, then applied homogeneously to each patient regardless of their unique genetic makeup.

An important subfield in precision medicine is pharmacogenetics, the study of how an individual’s genetics influence how a drug is metabolized and used. There have been numerous studies exploring how a specific gene can impact certain medications, and most of the research in this area has focused on identifying single genes that affect specific medications.

Aarhus Research Into Role of Genetic Variations in Drug Metabolism

As part of the study of genetic variations and drug metabolism, lead researcher Christiane Gasse, PhD (above) of Aarhus University, noted a significant finding. (Photo: Aarhus University)

New research from Aarhus University, recently published in Translational Psychiatry, analyzed the frequency of genetic variations that affect drug metabolism and drug targets in over 77,000 patients. Researchers found that over 80% of the study’s participants had more than three genetic variants that affect how each individual metabolizes medication.

“Pharmacogenetic variation can impact how we metabolize or react to drugs compared with the average patients,” Christiane Gasse, PhD, lead researcher in this study, said in a recent statement. “Rapid metabolism can increase the risk of a reduced effect of medicine, and slow metabolism can increase the risk of an ‘overdose’ that can be experienced as side effects.”

The combination of genetic variations may affect how each patient reacts to the drug, potentially causing side effects or affecting the medication’s efficacy. These genetic variations also may affect different medications in different ways. Pharmacological variations can make different doses of medications have effects that vary based on individuals and can make a medication last too long, or cause it to be absorbed too quickly.

Analysis Into Pharmacogenetic Variants and Documented Drug Dosage Adjustments

“The study has primarily analyzed pharmacogenetic variants with documented recommendations of dose adjustment having great importance for the effect of the affected drugs,” Gasse explained in the Aarhus University news release in June. “Many of these drugs are psychotropic medications—i.e. medicine for people with a mental disorder, but include also drugs for cardiovascular disorders. We found that more than 80% of the analyses population had more than three pharmacogenetic variants that potentially affect the metabolism of these drugs.”

Perhaps the most significant finding is the large number of genes that may play a role in drug metabolism for a single individual. Identifying the influence of a single gene on a medication can be complex, but factoring in many genes makes this task even more difficult.

“Most often there are several genes and genetic variants that influence the effect of the medicine,” Gasse said. “Within all medicinal products, we know of 42 variants where international pharmacogenetic consortia have described recommendations about pharmacogenetic guided dosing. They are therefore relevant for adjustments and are, therefore, relevant for clinical practice.

“The study demonstrates the need to use a pharmacogenetic test that analyzes a wide range of genes and genetic variants,” Gasse continued. “This can provide information about the choice of the right medicinal product or the right dose for the individual patient.”

The unique combination of multiple genes found to influence medication metabolism has significant implications for pharmacogenetics. Gasse’s team’s research shows that testing for pharmacogenetic considerations will likely be an important component of practicing precision medicine.

Genetic testing will likely play an important role in prescribing medications in the future, determining not only what medication is best for each patient, but also indicating individualized doses and frequencies. Pharmacogenetics will impact how medicine is practiced long into the future, and hospital systems that prepare for the future now will be best positioned to provide modernized care for their patients as precision medicine progresses.

—Caleb Williams

Related Information:

Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample

Testing several genes can lead to better effect of medicinal products