AmpliChip CYP450 Test
Encyclopedia
AmpliChip CYP450 Test is a clinical test from Roche
Hoffmann-La Roche
F. Hoffmann-La Roche Ltd. is a Swiss global health-care company that operates worldwide under two divisions: Pharmaceuticals and Diagnostics. Its holding company, Roche Holding AG, has shares listed on the SIX Swiss Exchange....

. The test aims to find the specific gene types (a genotype) of the patient that will determine how he or she metabolizes certain medicines, therefore guides the doctors to prescribe medicine for best effectiveness and least side effects.

The AmpliChip CYP450 Test uses micro array technology from Affymetrix
Affymetrix
Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...

 (GeneChip) to determine the genotype of the patient in terms of two cytochrome P450 enzymes: 2D6 and 2C19.

2D6 and 2C19 variability

CYP2D6
CYP2D6
Cytochrome P450 2D6 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds...

 and CYP2C19
CYP2C19
Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...

 belong to the Cytochrome P450 oxidase
Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...

 family. CYP2D6 has over 90 variants, 2C19 has mainly three. They are responsible for the majority of the inter-individual variability in the ability to metabolize drugs.

There are four phenotypes of CYP2D6: Poor Metabolizer (PM), Intermediate Metabolizer (IM), Extensive (normal) Metabolizer (EM) and Ultrarapid Metabolizer (UM). For CYP2C19, there are only two phenotypes: PM and EM. If a substrate of the enzyme is given to the patient as a medication, and if the patient has reduced CYP2D6 or CYP2C19 activity, the patient will have elevated drug concentration in their body, and therefore severe side effects may occur. On the other hand, for the UM patient, the drug concentration might be too low to have a therapeutic effect. So testing the phenotype of the patient is important to help determine the optimum dosage of the drug.

How Does It Work

The test analyzes the DNA of a patient to determine the genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...

, and prediction of the phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

 can then be made. The DNA sample comes from blood (as Roche suggests) or, alternatively, comes from a mouth brush called buccal swab
Buccal swab
A buccal swab is a way to collect DNA from the cells on the inside of a person's cheek. Buccal swabs are a relatively non-invasive way to collect DNA samples for testing. Buccal means cheek or mouth....

. The analysis has five steps after DNA is extracted from patient samples:
  1. PCR amplication of the gene.
  2. Fragmentation and labeling of the PCR product
  3. Hybridization and staining on the AmpliChip DNA microarray.
  4. Scanning the chip.
  5. Data analysis.

FDA Approval

FDA approved the test on December 24, 2004. The AmpliChip CYP450 test is the first FDA approved pharmacogenetic test.

Applications

Since a lot of the CYP2D6 substrates are psychiatric drugs (antidepressant and antipsychotics, for example), the AmpliChip CYP450 has been extensively used in psychiatry.

Criticism

The main criticism of the test is that the test finds out the genotype (the makeup of the gene types) of the patient, which does not necessarily cover all the phenotypes (the actual biological effect). For example, some argue that the so called ultra-rapid metaboliser, who has extra copies of the 2D6 gene expressed, cannot be reliably tested.

Also, the test does not cover some rarer genotypes, nor genotypes that have not yet been discovered.

Also, insurance companies still do not cover the price of the test, which can cost $600-$1300 to the patient, because the test is "experimental, investigational or unproven".

External links

Official Website: http://molecular.roche.com/assays/Pages/AmpliChipCYP450Test.aspx
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