Investigation of the effect of genetic variations on efficacy and side effects of pharmacological substances

Pharmacogenetics determines the influence of genetic variations on the response to drugs. Different stages of the way pharmaceutical substances must take in the body like uptake, metabolism, distribution, actions on target molecules and elimination are affected by genetic variations.  Metformin, the mostly used antidiabetic drug worldwide, is not metabolized in the body, so its efficacy and the occurrence of side effects is mostly regulated by uptake and elimination via transport proteins. Genetic variations decreasing the number of transport proteins lead to a lower (or no) response to Metformin and increase the odds to suffer from side effects. In contrast to Metformin, most pharmaceutical substances are metabolized in the body and so either activated or degraded. The most prevalent drug-metabolizing enzymes belong to the Cytochrome P450 family. Genetic variations activating, decreasing their activity, or deactivating its members are largely responsible for drug metabolism and response of up to 90% of available drugs. Genetic variations also determine the strength and type of effect pharmaceutical substances have if they occur in the substances target molecules. Mutations in the adenosine receptor determine if one feels awake, motivated with increased energy, or becomes a nervous wreck, suffers from tachycardia and counting sheep all night after consuming coffee. This not only influences our daily life but is important for persons on caffeine containing medications or athletes, using caffeine to enhance their performance. Even mutations in genes in microorganisms colonizing our body might have an impact, if these microorganisms – for example in the gut – create substances, which act therapeutically in our body. This determines if isoflavone rich medications have an effect in mellowing postmenopausal symptoms.

We investigate mutations in organic cation transporters and their effect on Metformin efficacy, to predict if additional medications or an adjustment of dose are needed to treat diabetes. Furthermore, we are interested in their effects on side effect prevalence which drastically diminishes compliance.

We investigate mutations in caffeine target genes and metabolizing enzymes to optimize dose recommendations for performance enhancement in athletes.

The Author
Natascha Schweighofer

Natascha Schweighofer, Mag. Dr. med. sci.

The COMET Center CBmed is funded within COMET – Competence Centers for Excellent Technologies by the Federal Ministry of Climate Action, Environment, Energy, Mobility, Innovation and Technology (BMK), the Federal Ministry for Digital and Economic Affairs (BMDW), Land Steiermark (Styrian Business Promotion Agency – SFG) and Land Wien (Vienna Business Agency – WAW). The COMET program is executed by the Austrian Research Promotion Agency (FFG).

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