Adjustment of dosage may be needed if you carry a common Neandertal gene variant
For a drug to be effective and not harmful it needs to be administered at the right dosage. Certain enzymes in the body eliminate drugs, and the activity of these enzymes vary between individuals. Researchers at the Max Planck Institute for Evolutionary Anthropology in Germany and Karolinska Institutet in Sweden have studied two enzymatic variants which eliminate drugs less efficiently and show that the these enzyme variants are inherited from Neandertals.
Precision medicine aims to customize health care, with treatments tailored to each patient. The hope is that patients are prescribed medications in the right dosage, appropriate to them, based on genetic and other factors. It is well known that genetic variants in the genes encoding enzymes in the cytochrome P450 family affect how efficient these enzymes are.
In the present study, published in The Pharmacogenomics Journal, a team of researchers discovered that two of the most important genetic variants influencing the the ability to eliminate drugs are inherited from Neandertals. These variants are carried by twenty percent of present-day Europeans.
The study, led by Hugo Zeberg, researcher at the Department of Neuroscience and Max Planck Institute for Evolutionary Anthropology, Karolinska Institutet, and Svante Pääbo, Director at the Max Planck Institute for Evolutionary Anthropology, identified a DNA segment inherited from Neandertals, carrying two cytochrome P450 enzymes. These enzymes eliminate several common drugs such as the blood thinner warfarin, the antiepileptic drugs phenytoin, the cholesterol lowering drugs statins and common painkillers such as ibuprofen. The Neandertal variants of the enzymes are generally less efficient at eliminating drugs.
"This is one case where the admixture with Neandertals has a direct impact in the clinic. Otherwise therapeutic doses can be toxic for carriers of the Neandertal gene variant", says Hugo Zeberg.
Neandertals were a group of archaic humans that populated Europe and Asia before the arrival of modern humans. When modern humans and Neandertals met 60,000 years ago, they mixed. As a result, people with roots outside Africa carry one to two percent of their genome from Neandertals.
The clinically relevant CYP2C8*3 and CYP2C9*2 haplotype is inherited from Neandertals.
Haeggström S, Ingelman-Sundberg M, Pääbo S, Zeberg H
Pharmacogenomics J 2022 Jul;():