Chip-Based Test for Broad Diagnostic Use

A new chip-based test analyzes variations in two genes that play a major role in the metabolism of many widely used drugs and therefore has many applications. The test has received the CE Mark.

This AmpliChip CYP450 test detects variations in the cytochrome P450 2D6 and 2C19 genes and provides the associated predictive phenotype: poor, intermediate, extensive, or ultra-rapid metabolizer. Doctors can use the results to help them select drugs and personalize doses for drugs primarily metabolized by the enzymes these genes encode. Enzymes encoded by the CYP2D6 gene metabolize many antidepressants, antipsychotics, anti-arrhythmics, pain drugs, anti-emetics, and beta-blockers. Enzymes encoded by the CYP2C19 gene metabolize drugs from a variety of classes, including anticonvulsants, proton pump inhibitors, anticoagulants, benzodiazepines, and antimalarials.

The test uses two industry gold standards: the polymerase chain reaction (PCR) amplification technology of Roche (Basel, Switzerland) and the high-density microarray technology of Affymetrix (Santa Clara, CA, USA). Affymetrix has announced that its GeneChip system 3000Dx instrumentation, on which the AmpliChip CYP450 test is run, has also received the CE Mark.

Poor metabolizers treated with drugs that are extensively dependent on certain "normal” enzyme activity are at increased risk for excessive or prolonged levels of the drug in their blood and toxicity, while ultra-rapid metabolizers may not achieve sufficient therapeutic levels in their blood with standard dosing. In the case of pro-drugs (drugs that require enzymatic action before they become the therapeutic compound in the body), the opposite phenomenon occurs. In addition, drugs taken at the same time and environmental factors such as diet can inhibit or induce cytochrome P450 enzyme activity.

To allow a highly accurate prediction of patient phenotype, the AmpliChip CYP450 test has the ability to detect not just the presence of CYP2D6 gene duplications but also to discern which variation of the gene (allele) has been duplicated. This specificity is important in correctly predicting the ultra-rapid metabolizer phenotype and avoiding misclassification of the patients tested.

"With the CE Mark for the AmpliChip CYP450 test, we are on our way to helping physicians move toward a more personalized approach to therapy, and to building our new line of chip-based diagnostics products,” said Heino von Prondzynski, head of Roche Diagnostics and member of the Roche executive committee.





Related Links:
Roche Diagnostics
Affymetrix