Feasibility of a Microarray-Based Point-of-CareCYP2C19Genotyping Test for Predicting Clopidogrel On-Treatment Platelet Reactivity

Abstract

Clopidogrel is a prodrug which is converted into active metabolite by cytochrome P450 isoenzyme,CYP2C19. Numerous polymorphisms ofCYP2C19are reported, and a strong link exists between loss-of-function (LOF) or gain-of-function polymorphisms, clopidogrel metabolism, and clinical outcome. Hence, a fully automated point-of-care CYP2C19 genotyping assay is more likely to bring personalized antiplatelet therapy into real practice. We assessed the feasibility of the Verigene 2C19/CBS Nucleic Acid Test, a fully automated microarray-based assay, compared to bidirectional sequencing, and performed VerifyNow P2Y12 assay to evaluate the effect ofCYP2C19polymorphisms on on-treatment platelet reactivity in 57 Korean patients treated with clopidogrel after percutaneous coronary intervention. The Verigene 2C19/CBS assay identified *2, *3, and *17 polymorphisms with 100% concordance to bidirectional sequencing in 180 minutes with little hands-on time. Patients were classified into 4 groups: extensive (*1/*1;n=12, 21.1%), intermediate (*1/*2, *1/*3;n=33, 57.9%), poor (*2/*2, *2/*3, and *3/*3;n=11, 19.3%), and ultrarapid metabolizers (*1/*17;n=1, 1.8%). The prevalence of theCYP2C19  *2, *3, and *17 alleles was 36.0%, 12.3%, and 0.9%. Platelet reactivity showed gene dose response according to the number ofCYP2C19LOF allele. In conclusion, the Verigene 2C19/CBS assay gave accurateCYP2C19genotype results which were in well match with the differing on-treatment platelet reactivity.