CYP450 genotyping for determining drug metabolizer status.

The AmpliChip CYP450 test (Roche Molecular Systems, Pleasanton CA) is a drug metabolizing enzyme (DME) genotyping system that detects genetic variations (polymorphisms) in two CYP450 genes, CYP2D6 and CYP2C19, using deoxyribonucleic acid (DNA) extracted from patients’ blood. It is used with the GeneChip System 3000Dx microarray platform developed by Affymetrix (Santa Clara CA). The test is conducted in a laboratory specializing in genetic analysis, and involves polymerase chain reaction (PCR) amplification of selected DNA segments. The PCR products are fragmented, labelled, and hybridized to the microarray, then stained to produce fluorescent signal intensities that are captured by a laser scanner. The hybridization pattern is analyzed using software, to identify the CYP2D6 and CYP2C19 variations present. The resultant genotype and predicted phenotype are reported for each clinical sample. The AmpliChip test queries for 31 polymorphisms and mutations, including gene deletions and duplications; and for CYP2D6, discerns which variation of the gene (allele) has been duplicated. AmpliChip was developed as a diagnostic tool for physicians, to aid in the identification of the following CYP2D6 metabolizer phenotypes: poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM), or ultrarapid metabolizer (UM); and of the CYP2C19 phenotypes (PM or EM). The test is intended to help physicians with drug selection and individualization of drug therapy.