Testing several genes can provide precise knowledge about the choice of right medicinal products

Most of us have genetic variations that increase the risk of medicinal products not being effective. In order to provide a more effective treatment with fewer side effects, we need to analyze more of these genetic variations. This will provide us with more precise knowledge about how the individual patient reacts to medicinal products. A new research result from Aarhus University shows that.

Personalized medicine has been a hot topic in recent years, using information about the genes to adapt the treatment to the individual patient. Personalized medicine potentially provides better treatment and fewer side effects for the patient. At least in an ideal world.

How the body converts medicinal products - the scientific term is metabolizes - is also affected - among other factors - by our genes, among other factors. Research from Aarhus University now shows that more than eighty per cent of the participants in a study based on data from the National Psychiatry Project iPSYCH, have more than three genetic variants, which increase the potential risk of the medicinal products not having the effect they should.

"Pharmacogenetic variation can impact how we metabolize or react to drugs compared with the average patients. 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," explains Christiane Gasse from Aarhus University, who is leading the study.

Not only applicable to medicine for mental disorders

The researchers have analyzed the frequency of genetic variants in clinically relevant drug metabolism or drug targets of 51,464 people with a diagnosed mental disorder and 26,220 without - a total of 77,684 people.

The study has primarily analyzed pharmacogenetic variants with documented recommendations of dose adjustment having great importance for the effect of the affected drugs. 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 analyzed population had more than three pharmacogenetic variants that potentially affect the metabolism of these drugs."

Christiane Gasse from Aarhus University

Criteria for how the medication and dose work most effectively on the majority of the population defines the dosage of a medicine. However, the desired effect is not achieved in some cases, or or patients experience side effects. Individualized treatment with medicinal products may include a pharmacogenetic test, in which the patient's genes are analyzed. Based on the patient's genetic profile, it is possible to determine how effectively the actual medicine is metabolized in the individual patient.

"Most often there are several genes and genetic variants that influence the effect of the medicine. 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," explains Christiane Gasse.

Now, genetic tests often analyze a single genetic variation, which is known to have an effect on the metabolism of the drug in question. However, the researchers believe that it would be possible to obtain far more accurate information about the patient's disposition to metabolize medicines, if more genetic variants were analyzed.

The solution is a wide-ranging panel test that can analyze several pharmacogenetic variations at the same time and in this way provide the opportunity to plan more optimal treatment.

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

She adds that a pharmacogenetic test can either be performed prior to the first treatment with a relevant drug, and can be used as guidance for the planned and future treatments, or it can be done during the course of treatment with aim to adjust the dose and if needed the medicine.

Source:
Journal reference:

Lunenburg, C.A.T.C., et al. (2021) Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample. Translational Psychiatry. doi.org/10.1038/s41398-021-01417-4.

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