Establishment of a CYP2C19 genotyping assay for clinical use.
Conversion of clopidogrel (Plavix) to its active metabolite is catalyzed largely by the P450 enzyme 2C19 (CYP2C19). Numerous allelic variants of CYP2C19 exist. The *1 allele is considered wild type, whereas the *2 and *3 alleles have no in vivo enzymatic activity. Conversely, the *17 allele has increased expression, resulting in increased clopidogrel activation. Poor metabolizers (*2/*2 and *2/*3 genotypes) experience higher rates of therapeutic failure. For this reason, we have validated a CYP2C19 genotyping assay for the *1, *2, *3, and *17 alleles. Genomic DNA extracted from 30 deidentified EDTA whole-blood samples from patients was analyzed at 2 independent facilities using specific TaqMan realtime polymerase chain reaction primers and probes. Concordant genotypes were generated on all samples tested. Of the 30 samples, 15 were CYP2C19*1/*1, 8 were CYP2C19*1/*17, 5 were CYP2C19*1/*2, and 2 were CYP2C19*2/*17. There were no CYP2C19*3 alleles or *2/*2 homozygous genotypes detected. This CYP2C19 genotyping assay is appropriate for clinical testing, demonstrating excellent interlaboratory concordance, enabling the selection of the most effective clopidogrel treatment regimen for patients undergoing percutaneous coronary intervention.
Department of Pathology, The Geisel School of Medicine at Dartmouth, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA. mark.a.cervinski@hitchcock.org
Mark A
MA
Cervinski
Mary C
MC
Schwab
Joel A
JA
Lefferts
Lionel D
LD
Lewis
Kimberly A
KA
Lebel
Allison M
AM
Tyropolis
Solveig M V
SM
Pflueger
Gregory J
GJ
Tsongalis
D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000097:blood / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004247:DNA / Q000032:analysis; D015894:Genome, Human; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D004247:DNA; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine