Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Clopidogrel Treatment [T88.7]

OMIM numbers: 609535, 124020 (CYP2C19)

Dipl.-Biol. Birgit Busse

Scientific Background

Clopidogrel is a prodrug that is converted into an active metabolite in the body. Several cytochrome P450 enzymes are involved in this reaction. The conversion of clopidogrel into 2-oxo-clopidogrel is catalyzed mainly by CYP1A2, CYP2C19 and CYP2B6; further conversion into the active metabolite mainly through CYP3A4, CYP2C19, CYP2B6 and CYP2C9. Variants in the genes of the involved enzymes that lead to a reduced enzyme activity may result in a clopidogrel resistance. Compared to persons with unimpaired metabolism capacity, carriers of inactivating CYP2C19 variants exhibit reduced inhibition of thrombocyte aggregation as well as a higher risk for cardiovascular incidents (e.g. stent thrombosis, stroke or cardiac infarction) when treated with clopidogrel. For affected patients a dosage adjustment or a change in medication (e.g. prasugrel, acetylsalicylic acid) can be taken into consideration. Due to CYP2C19 being involved in both conversion reactions, variants in the CYP2C19 gene are of major significance for the efficacy of treatment. When required, the other enzymes can be tested as well. Information regarding the association of CYP2C19 genotypes and clopidogrel resistance are by now included in the prescribing information.