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Gene Chips to Detect CYP Variations: A New Step Toward Customized Medical Therapy.

abolize particular medications. As a result, patients can be classified as poor, intermediate, extensive, or ultra-rapid metabolizers. These conditions are relatively common, with prevalences that vary across different races. Similar to the scenarios described above, these patients are at risk for abnormal blood concentrations: poor metabolizers may develop serious side effects, and extensive or ultra-rapid metabolizers may be insufficiently treated.

Recent advances in microarray (gene chip) technology have made it possible to screen patients thoroughly for genetic variations in CYP enzymes. The AmpliChip CYP450 Test (Roche Diagnostics) detects mutations in two important CYP subtypes. The first, CYP2D6, metabolizes a number of medications, including antidepressants, anti-psychotics, anti-arrhythmics, and beta-blockers. The second, CYP2C19, metabolizes anticoagulants, anticonvulsants, proton pump inhibitors, benzodiazepines, anti-malarials, and other medications. The literature has shown that a genotype screen, such as the AmpliChip CYP 450 Test, can detect up to 90% of poor metabolizers at risk for overdoses.

High density microarrays, such as the one used by the AmpliChip CYP450 test, provide a versatile, miniaturized means to screen for multiple nucleic acid products in a rapid and parallel fashion. To build the microarray, small DNA fragments, also called probes, are anchored and synthesized at specific locations on a small, coated quartz surface. Different probes can be attached to different locations. Each probe is chosen to hybridize selectively with a specific DNA fragment. In the case of AmpliChip CYP450 test, this provides the ability for particular probes to bind portions of wild-type or mutant sequences from CYP2D6 and CYP2C19. The microarray is also constructed in a way that can detect duplications of a particular allele.

The actual test is carried out with a patient blood sample. The first step is to amplify CYP2D6 an
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