Ancient Neanderthal gene variants can slow drug metabolism
New research led by scientists from the Max Planck Institute for Evolutionary Anthropology has traced two genetic variants to our Neanderthal relatives that can affect how well drugs are metabolized. It is hypothesized these ancient Neanderthal genes may account for some differences in therapeutic drug activity from person to person.
While us Homo sapiens are currently the only species of human inhabiting the Earth, that wasn’t always the case. For hundreds of thousands of years, a whole family of related humans shared the planet from mysterious “ghost” species and Denisovans, to the more commonly known Neanderthals.
Homo sapiens may have won the evolutionary battle in the end, there are many traces of these other species in our DNA. You see, modern humans apparently got along very well with different species at various time in history, and traces of Neanderthal DNA can still be found in many people around the world.
Sometimes these ancient Neanderthal genes can be beneficial. A 2020 study, for example, found one in three European women carried a Neanderthal gene variant that codes for progesterone receptors. This meant those women were likely to experience lower rates of miscarriage and increased fertility.
But sometimes these Neanderthal genes are less helpful, as highlighted in this new study which identified a pair of variants linked to decreases in drug metabolism. The two Neanderthal gene variants reduce the activity of key enzymes that metabolize a number of different drugs.
The research indicates carriers of these gene variants may be “slow metabolizers,” and are likely to demonstrate decreased metabolism of drugs. This includes “antidiabetic drugs (e.g., pioglitazone), statins (e.g., cerivastatin), anti-inflammatory drugs (e.g., ibuprofen) and chemotherapeutic agents (e.g., paclitaxel).”
Hugo Zeberg, lead researcher on the study, said there are possible clinical implications for carriers of these genetic variants. Standard doses of drugs such as blood-thinner warfarin and anticonvulsant phenytoin could become toxic in some people with certain kinds of low enzymatic activity.
"This is one case where the admixture with Neanderthals has a direct impact in the clinic,” said Zeberg. “Otherwise therapeutic doses can be toxic for carriers of the Neanderthal gene variant.”
It is estimated around 12 percent of people in Europe could carry these genetic variants. The researchers ultimately don’t indicate these findings should directly influence clinical practice, but instead can be used to help explain how different ancestries can effect therapeutic outcomes.
The new study was published in The Pharmacogenomics Journal.
Source: Karolinska Institutet
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