CYP2C19 Gene Detection Kit

The cytochrome P450 (CYP) family of enzymes performs the primary metabolism of many drugs in the human body. One of these CYP enzymes, CYP2C19, is responsible for the metabolism of a wide variety of drugs including the anti-blood clotting drug Plavix (Clopidogrel). CYP2C19 is required to convert Plavix, a prodrug, to its active form. Patients who have poor CYP2C19 activities will not effectively convert Plavix to its active form. Plavix will have low efficacy in those patients in preventing heart attack, stroke, and cardiovascular death. The Food and Drug Administration (FDA) added a boxed warning to the label of Plavix, alerting patients and doctors of the reduced effectiveness in patients who are poor metabolizers of Plavix (poor CYP2C19 activities)1. It is estimated that 2 to 14% of the population are poor metabolizers; the rate varies based on racial background.

The drug levels and antiplatelet effects of Plavix differ depending on the genotype of the CYP2C19 enzyme. The following represent the different alleles of CYP2C19 that make up a patient's genotype1:

• The CYP2C19*1 allele has fully functional metabolism of Plavix.
• The CYP2C19*2 and *3 alleles have no functional metabolism of Plavix. These two alleles account for most of the reduced function alleles in patients of Caucasian (85%) and Asian (99%) descent classified as poor metabolizers.
• The CYP2C19*4, *5, *6, *7, and *8 and other alleles may be associated with absent or reduced metabolism of Plavix, but are less frequent than the CYP2C19*2 and *3 alleles.
• A patient with two loss-of-function alleles (as defined above) will have poor metabolizer status.
• The CYP2C19*17 allele identifies individuals who may be enhanced metabolizers of drugs. A recent report indicates increased risk for bleeding in individuals treated with Plavix who carry the *17 allele2.

• References

  Sibbing D et al. (2010). Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in Clopidogrel-treated patients with coronary stent placement. Circulation. 121:51