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New genetic discovery could reduce the guesswork in drug dosing
Date:10/1/2013

ndividual is a poor or ultra-rapid metabolizer. The SNPs we found will more precisely predict whether an individual is in the ultra-rapid or intermediate metabolic range," Wang said. "The poor metabolizers are well-defined by the current panel with variants with no enzyme activity at all."

A poor metabolizer is likely to experience high toxicity from medications processed by this enzyme, or get minimal or no benefit at all if a drug such as codeine needs to be activated by it. Ultra-rapid metabolizers, on the other hand, may not benefit from drugs processed by the enzyme or suffer adverse reactions from drugs that need it for activation. Metabolizer status has pronounced effects on treatment outcomes and cost of therapy.

"If you could give a drug and get an immediate response, then that in itself would be a marker for the drug's effect. But there is no immediate response for many drugs," Sadee said. "Having a pharmacogenomics marker test that's viable and useful could predict when caution is needed in prescribing drugs."

In the case of antidepressants or antipsychotics, for example, with delayed clinical effect, an ultra-rapid metabolizer would have to take the drug for weeks before finding out that a drug isn't having any effect, while a poor metabolizer is likely to have toxic side effects. And with codeine, which is converted into morphine in the body, an ultra-rapid metabolizer could inadvertently overdose on morphine by taking too much codeine.

The Ohio State pharmacogenomics group is among the few in the world pursuing hard-to-find genetic variants that significantly alter biological functions. For the past 30 years, scientists studying genetic variants have focused on genetic variants that change enzyme function by altering the encoded amino acid sequence.

Sadee's lab, however, focuses on variants that are harder to detect and analyze because they have no direct role in determining the protein sequence; they exist
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Contact: Wolfgang Sadee
wolfgang.sadee@osumc.edu
614-292-1597
Ohio State University
Source:Eurekalert

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