Drug Prescriptions may be Made More Accurate by Gene Mutation in Liver Cells

A new American study says that a tiny gene mutation in human liver cells might help indicate proper dosage for half of all drugs.

The study has been published online in The Pharmacogenomics Journal.

Researchers at Ohio State University and colleagues have identified this mutation, and have shown that it alters the level of a protein in the liver responsible for processing between 45 per cent and 60 per cent of medications used to treat a wide range of conditions.

Each gene contains two alternative forms - called alleles - that are identical in most people.

However, in this case, the researchers found that the activity level, or expression, of one allele differs from its partner allele in a single gene.

That small difference is called a single nucleotide polymorphism, or SNP.

This SNP affects the gene's protein-producing process, in turn lowering the level of an enzyme known as CYP3A4.

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The faster a drug is processed, or metabolized, by this enzyme in the liver, the more quickly it is eliminated from that tissue and the body as a whole.

When this enzyme level is lowered by the presence of this SNP, people are likely to require smaller doses of medicines that the enzyme metabolizes.

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But this also means that higher doses of these same drugs can be dangerous to people with the mutation if those levels become toxic.

The study further showed that people with the mutation who take a certain class of cholesterol-lowering drugs do indeed require lower doses of these medications to achieve the same effect that higher doses produce in people without the SNP.

The researchers suggest that this mutation could serve as a molecular biomarker to aid doctors in clinical practice, affecting dosing requirements, patients' response to medications and toxicity levels of numerous drugs, especially anti-cancer medications.

Lead author Danxin Wang, a research scientist and adjunct assistant professor of pharmacology at Ohio State, said: "With some cancer drugs, there is a very narrow therapeutic index, meaning that if doctors give patients a slightly higher dose, it will cause toxicity. We believe this same biomarker could be used to predict that toxicity threshold in cancer patients."

Wang noted that using this SNP as a biomarker could reduce the guesswork associated with prescribing drugs.

Wang said: "Right now, because there are no biomarkers available to predict CYP3A4 activity, trial and error determines whether cholesterol goes down with the prescribed dose.

"You never know who has what enzyme level, so you never really know what dose to give an individual if you don't have a biomarker."

Source-ANI
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