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

linical biomarker test.

The research is published online in the journal Human Molecular Genetics.

The study included a clinical trial of 164 children, about one-third of whom were African American. The results show that these two variants are common in both Caucasians and African Americans, and confirmed that the variants influence how patients metabolize the cough suppressant dextromethorphan.

Being able to apply this testing to more than one ethnic group is significant, Sadee said, because most current dosing decisions are made based on genetic findings in only whites.

The findings suggested that about one-third of people would be expected to have lower enzyme activity, and therefore slower, or intermediate, drug metabolism not so low that they are poor metabolizers. Another 6 percent would have higher enzyme activity and be categorized as ultra-rapid metabolizers. Only by testing for these variants would clinicians know for sure.

The variants were found by lead author Danxin Wang, a research scientist and adjunct associate professor in pharmacology at Ohio State. They are called single-nucleotide polymorphisms, or SNPs (pronounced "snips").

Each gene contains two alternative forms called alleles that are functionally identical in most people. However, in some cases, the activity level, or expression, of an allele can differ from its partner allele in a single gene. That difference the genetic variant, or SNP affects the function of the protein or enzyme produced by that gene.

Wang used liver tissue samples from Caucasians to conduct the analyses that identified where these two functional variants are located on the CYP2D6 gene. The clinical trial testing these variants' effects against dextromethorphan is just the beginning the researchers hope to expand these trials with multiple drugs and eventually enter clinical biomarker tests.

"The current panel can determine whether an i
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Contact: Wolfgang Sadee
wolfgang.sadee@osumc.edu
614-292-1597
Ohio State University
Source:Eurekalert

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